Brosura Abstracte Conferinta de Imuno-Onco-Dermatologie, 18-21 Septembrie 2019

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A 3-a Conferință
a Asociației
de Imuno-Dermatologie
-----------------------------------------
A 48-a Conferință
a Societății de Imunologie
din România
18-21 septembrie 2019

Hotel Caro, București
www.imuno-dermatologie.ro/conferinta3
Management logistic și Comunicare
Partener Gold
d e v e l o pment
Parteneri Silver
Parteneri
Fundaţia pentru Medicinã

Celularã şi Molecularã
P
din România
Proton Impex 2000
Parteneri media
#5BB1BC - #0B8595
#0B8595 #86CCD2
R:11 G:133 B:149 R:91 G:177 B: 188 R:11 G:133 B:149
R:134 G:204 B:210
C:84% M:32% Y:36% K:4% C:63% M:12% Y:25% K:0% C:84% M:32% Y:36% K:4%
C:46% M:2% Y:18% K:0%
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CUPRINS
ORGANIZATORI 04
PROGRAM ȘTIINȚIFIC 06
ABSTRACTE
• Miercuri, 18 septembrie 18
• Joi, 19 septembrie 62
• Vineri, 20 septembrie 79
• Sâmbătă, 21 septembrie 101
18-21 septembrie 2019 3

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ORGANIZATORI
Comitet Științific Conf. Univ. Dr. Laslo Fekete
Conf. Univ. Dr. Simona Ianoși
Prof. Univ. Dr. Robert Ancuceanu SL. Dr. Gabriel Ianoși
Conf. Univ. Dr. Flavia Baderca Prof. Univ. Dr. Cătălin Marian
SL. Dr. Camelia Berghea CSI Dr. Monica Neagu
Conf. Univ. Dr. Florian Berghea Conf. Univ. Dr. Carolina Negrei
Conf. Univ. Dr. Daniel Boda CSII Dr. Gabriela Neagu
Prof. Univ. Dr. Daciana Brănișteanu Prof. Univ. Dr. Giovanni Pelacani
Dr. Lorelei Brașoveanu Prof. Univ. Dr. Gabriela Radulian
Prof. Univ. Dr. Roxana Bumbăcea Prof. Univ. Dr. Maria Rotaru
Prof. Univ. Dr. Daniela Călina SL. Dr. Emilia Rusu
Prof. Univ. Dr. Petru Cianga Prof. Univ. Dr. Demetrios Spandidos
Conf. Univ. Dr. Costin Căruntu Dr. Crina Stăvaru
CSII Dr. Carolina Constantin SL. Dr. Gabriela Stoleriu
Prof. Univ. Dr. Ileana Constantinescu SL. Dr. Mircea Tampa
Prof. Univ. Dr. Rodica Cosgarea Prof. Univ. Dr. Cristiana Tănase
Prof. Univ. Dr. Marieta Costache Prof. Univ. Dr. Alin Tatu
Prof. Univ. Dr. Victor Cristea Prof. Univ. Dr. Aristidis Tsatsakis
Conf. Univ. Dr. Patricia Cristodor Prof. Univ. Dr. Coriolan Ulmeanu
Prof. Univ. Dr. Cristina Deheleanu Conf. Univ. Dr. Loredana Ungureanu
Prof. Univ. Dr. Diana Deleanu CSII Dr. Cornel Ursaciuc
Prof. Univ. Dr. Carmen Diaconu Asist. Univ. Dr. Vlad Voiculescu
SL. Dr. Anca Docea Prof. Univ. Dr. Sabina Zurac
Comitet Organizare Dr. Gheorghța Isvoranu

Dr. Harillaq Kaleshi
Conf. Univ. Dr. Daniel Boda Dr. Andreea Roxana Lupu
Dr. Marinela Bostan Drd. Adriana Narcisa Munteanu
Dr. Maria Bratan Prof. Univ. Dr. Monica Neagu
Conf. Univ. Dr. Constantin Căruntu Dr. Irina Radu
Prof. Univ. Dr. Ileana Constantinescu Drd. Mihaela Surcel
Dr. Adriana Diaconeasa CSII Dr. Cornel Ursaciuc
Asist. Univ. Dr. Mihaela Ghiță
4 18-21 septembrie 2019

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MIERCURI, 18 .09.2019: „Imunologia (tot) mai aproape de adevăr”
09.00–09.15 Deschiderea oficială
09.15–09.45 Conferință plenară

Moderator: Dr. Cornel Ursaciuc, Vice-Președinte Societatea de Imunologie din România, București
Boli rare ale adultului – starea de sănătate a pacienților cu imunodeficiență comună variabilă
Prof. Univ. Dr. Victor Cristea
UMF „Iuliu Hațieganu”, Cluj-Napoca, Președinte Societatea de Imunologie din România
09.45-10.00 Prezentarea Asociației Române a Pacienților cu Imunodeficiențe Primare

Artemiza Baldea
Președinte Asociația Română a Pacienților cu Imunodeficiențe Primare

Moderator: Prof. Univ. Dr. Monica Neagu, INCD „Victor Babeș”, București; Facultatea de Biologie,
Universitatea din București; Sp. Clinic Colentina, București
Early KLRG1+ but not CD57+CD8+ T Cells in Primary CMV Infection Predict Effector Function
and Viral Control
Prof. Univ. Dr. Iulia Popescu
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine,
University of Pittsburgh School of Medicine, Pittsburgh, USA
10.30-10.45 Pauză
10.45-11.15 Conferință plenară

Moderator: Prof. Univ. Dr. Victor Cristea, UMF „Iuliu Hațieganu”, Cluj-Napoca; Președinte
Societatea de Imunologie din România
Pattern-ul imun în melanomul cutanat

Prof. Univ. Dr. Monica Neagu
INCD „Victor Babeș”, București; Facultatea de Biologie, Universitatea din București; Sp. Clinic
Colentina, București
11.15–12.30 Prezentări orale: Imunologie fundamentală

Moderatori: Prof. Univ. Dr. Carmen Chifiriuc, Facultatea de Biologie, Universitatea din București &
CSII Dr. Carolina Constantin, INCD „Victor Babeș”, București;
Sp. Clinic Colentina, București
Rolul celulelor Langerhans în dermatologie
Manole Cojocaru
Facultatea de Medicină, Universitatea „Titu Maiorescu”, București
Haplotipurile HLA și dezechilibrele de înlănțuire în Nord-Estul României și în Europa
Mariana Pavel-Tanasă, Corina Cianga1,2, Daniela Constantinescu1,2, Camelia Mihailă2, Petru Cianga1,2
Dep. Imunologie, UMF „Grigore T. Popa” Iaşi; 2Lab. Imunologie, Sp. „Sf. Spiridon”, Iași
1
Modularea răspunsului imun în diabetul zaharat

Manuela Ciocoiu1, Magda Bădescu1, Daniela Jitaru2, Iris Bararu-Bojan1, Maria Cristina Vlădeanu1,
Codruța Bădescu3
1
Dep. Fiziopatologie, UMF „Grigore T. Popa” Iași; 2Inst. Regional de Oncologie, Iași;
3
Dep. Medicină Internă, UMF „Grigore T. Popa” Iași

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Studiul in vitro al efectului indus de MnCl2

Ştefania Lascăr1, Irina Elena Ionescu1, Raluca Elena Lăzărescu1, Vlad Tofan1, Mihaela Diaconu1,2,
Cătălin Țucureanu1, Ana Șerbănescu, Crina Stăvaru1, Adrian Onu1,3
1
INCDMM „Cantacuzino”, București; 2Facultatea de Biologie, Universitatea din București;
3
Facultatea de Farmacie, Universitatea „Titu Maiorescu”, Bucureşti
Interleukinele 1-41: Roluri pro- și antitumorale

Ovidiu Farc, Victor Cristea
Dep. Imunologie, UMF „Iuliu Hațieganu”, Cluj-Napoca
12.30-13.30 Pauză de prânz

Moderatori: Prof. Univ. Dr. Marieta Costache, Facultatea de Biologie, Universitatea din București &
Prof. Univ. Dr. Cristiana Tănase, INCD “Victor Babeș” București; Univ. “Titu Maiorescu”, Inst.
Cajal, București
O modificare de dogmă în imunologie
Prof. Univ. Dr. Petru Cianga, Corina Cianga
UMF „Grigore T. Popa”, Iași; Lab. Imunologie, Sp. „Sf. Spiridon”, Iași
14.00–15.30 Prezentări orale: Imunologie clinică
Moderatori: Conf. Univ. Dr. Elod Nagy, UMFST Târgu Mureș &
CSII Dr. Crina Stăvaru, INCDMM „Cantacuzino”, București
Implicarea imunologică a bolii celiace în patogenia accidentului vascular cerebral ischemic și
a neuropatiei periferice
Inimioara Mihaela Cojocaru
UMF „Carol Davila”; Sp. Clinic Colentina, București
Expresia receptorilor „Checkpoint” B7 și a liganzilor lor în leucemia mieloidă acută

Ion Antohe1,2, Angela Dăscălescu1,2, Cătălin Dănăilă1,2, Amalia Tițieanu1,2, Mihaela Zlei3, Iuliu Ivanov4,
Adriana Sireteanu4, Mariana Pavel-Tanasă5, Petru Cianga5,6
1
Dep. Hematologie, UMF „Grigore T. Popa” Iaşi; 2Dep. Hematologie, Inst. Regional de Oncologie, Iași;
3
Dep. Imunofenotipare, Inst. Regional de Oncologie, Iași; 4Dep. Diagnostic Molecular, Inst. Regional de
Oncologie, Iași; 5Dep. Imunologie, UMF „Grigore T. Popa” Iaşi; 6Lab. Imunologie, Sp. „Sf. Spiridon”, Iași
Profilul citokinelor în parodontita marginală cronică

Elena Tâlvan, Victor Cristea, Manuela Mihalache
UMF „Iuliu Hațieganu”, Cluj-Napoca
Profilul citokinelor în pneumonia acută comunitară

Raluca-Elena Tripon, Victor Cristea
Expresia ARN în boala parodontală

Elena Tâlvan, Victor Cristea, Cornelia Braicu, Ioana Berindan Neagoe
Interleukinele 19 și 33 în biologie și patologie

Ovidiu Farc, Victor Cristea
Dep. Imunologie, UMF „Iuliu Hațieganu”, Cluj-Napoca
Evaluarea procesului de transdiferențiere spre celule β pancreatice prin analiză proteomică
Radu Albulescu1,2, Daniela Lixandru3, Simona Dima3, Irit Meyvar1, Laura Georgiana Necula1,4,
Cristiana Tănase1,5
1
Universitatea „Titu Maiorescu”, Inst. Cajal, București; 2ICCF, București; 3Inst. Clinic Fundeni, București;
4
Inst. Virusologie „Ștefan S. Nicolau”, București; 5INCD „Victor Babeș”, București
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Populații și subpopulații de limfocite și celule dendritice în psoriazis

Mihaela Surcel1,2, Adriana Narcisa Munteanu1,2, Carolina Constantin1,3, Gheorghița Isvoranu1,
Ioana Ruxandra Pîrvu1, Adina Claudia Ionescu1,2, Gabriela Coman4, Vlad Voiculescu5,
Teodora Supeanu6, Mihail Alecu4, Cornel Ursaciuc1, Monica Neagu1,2,3
1
INCD „Victor Babeș”, București; 2Facultatea de Biologie, Universitatea din București;
3
Sp. Clinic Colentina, București; 4Sp. Clinic de Boli Infecțioase și Tropicale „Dr. Victor Babeș”, București;
5
UMF „Carol Davila”, București; 6Lab. Cercetare, ROMVAC SA, România

Moderator: Prof. Univ. Dr. Cristiana Tănase,
INCD „Victor Babeș”, București; Universitatea „Titu Maiorescu”, Inst. Cajal, București
Inflamația și semnalizarea Wnt în osteoartrită

Conf. Univ. Dr. Elod Nagy, Horváth Emőke
UMFST Târgu Mureș; Sp. Clinic Județean de Urgență Târgu Mureș
16.00-16.15 Pauză
16.15–18.15 Sesiune plenară: „Vaccinuri”

Moderatori: CSI Dr. Adrian Onu, INCDMM „Cantacuzino”, București &
Prof. Univ. Dr. Victor Cristea, UMF „Iuliu Hațieganu”, Cluj-Napoca,
Președinte Societatea de Imunologie din România
Scopurile biologice ale vaccinării

Corina Cianga, Petru Cianga
UMF „Grigore T. Popa”, Iași; Lab. Imunologie, Sp. „Sf. Spiridon”, Iași
Complexitatea dezvoltării vaccinurilor prin cercetare translațională: de la concept la evaluare

preclinică
Adrian Onu1,2, Norica Nechita3, Crina Stăvaru1, Gheorghe Săvuță4, Yuksel Rasit5,
Mihaela Ghergiceanu6
1
INCDMM „Cantacuzino”, București; 2Universitatea „Titu Maiorescu”, Facultatea de Farmacie, Bucureşti;
3
Institutul de Biochimie, București; 4Universitatea de Științe Agricole și Medicină Veterinară, Facultatea
de Medicină Veterinară “Ion Ionescu de la Brad”, Iași; 5ICCF, București; 6INCD „Victor Babeș”, București
Diferențierea și maturarea celulelor dendritice din măduvă osoasă murină – diferența între
organele proaspăt recoltate și crioprezervate
Irina Elena Ionescu1, Iuliana Caras-Scorțar1, Catălin Țucureanu1, Raluca Elena Lăzărescu1,
Ștefania Lascăr1, Ana Șerbănescu1, Adrian Onu1,2, Crina Stăvaru1
1
INCDMM „Cantacuzino”, București; 2Universitatea „Titu Maiorescu”, Facultatea de Farmacie, Bucureşti
Caracterizarea prin spectrometrie de masă a antigenelor vaccinale - aplicare la fragmentarea

virusului gripal
Cătălin Țucureanu1, Vlad Vasilca1, Vlad Tofan1, Alina Lengel1, Mihaela Lazar1, Adriana Costache1,
Crina Stăvaru1, Adrian Onu1,2
1
INCDMM „Cantacuzino”, București; 2Universitatea „Titu Maiorescu”, Facultatea de Farmacie, Bucureşti
Optimizarea expresiei bacteriene a antigenelor din candidații de vaccin – aplicații la vaccinul

gripal
Laura Andreea Ermeneanu1, Vlad Tofan1, Cătălin Țucureanu1, Vlad Vasilca1, Alina Lengel1, Adriana
Costache1, Crina Stăvaru1 și Adrian Onu1,2
1
INCDMM „Cantacuzino”, București; 2Universitatea „Titu Maiorescu”, Facultatea de Farmacie, București
Evaluarea markerilor de diagnostic pentru infecția cu virusul rujeolos în contextul unei

epidemii în România
Cătălina Pascu, Carmen Maria Cherciu, Maria Elena Mihai, Mihaela Lazăr
INCDMM „Cantacuzino”, București
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Principale obiective în producerea de vaccinuri/adjuvanți și introducerea/menținerea lor pe

piață. Reglementări
Yuksel Rasit1, Mariana Văduva2
1
ICCF București; 2INCDMM „Cantacuzino”, București
18.15–19.00 Prezentare postere
Efectele anti-tumorale ale unor compuși naturali în cancerul sferei ORL

Marinela Bostan1,2, Georgiana Gabriela Petrică-Matei3, Gabriela Ion1, Mirela Mihăilă1,
Camelia Hotnog1, Viviana Roman1, Lorelei Irina Braşoveanu1
1
Inst. Virusologie „Ștefan S. Nicolau”, Centrul de Imunologie, București; 2INCD „Victor Babeș”, București;
3
Dep. Citogenetică, Personal Genetics-Medical Genetics Center, București
Modificări morfopatologice induse de intoxicația acută cu MnCl2 pe model murin

Claudiu Gal1, Mariana Văduva1, Mihaela Diaconu1,2, Crina Stăvaru1
1
INCDMM „Cantacuzino”, București; 2Facultatea de Biologie, Universitatea din București
Celulele NK în diabet – caracteristici fenotipice
Gheorghiţa Isvoranu1, Emilia Manole1, Mihaela Surcel1,2, Adriana Narcisa Munteanu1,
Ioana-Ruxandra Pîrvu1, Monica Teodora Neagu1,2
1
INCD „Victor Babeș”, București; 2Facultatea de Biologie, Universitatea din București
Evaluarea activității antitumorale a extractului alcoolic din Tamarix Gallica din România
Ioana Mădălina Pitica1, Lilia Matei1, Laura Denisa Dragu1, Cristian Coman2,
Mihaela Economescu-Chivu1, Irina Alexiu1, Laura Georgiana Necula1, Cristina Mambet1,
Ana Neagu1, Saviana Nedeianu1, Carmen C. Diaconu1, Iuliana Crisan3, Coralia Bleotu1
1
Inst. Virusologie „Ștefan S. Nicolau”, București; 2INCDMM „Cantacuzino”, București;
3
S.C. HOFIGAL Export Import SA, București
Activitatea imunomodulatoare a extractului din Chelidonium Majus L.
Ioana Mădălina Pitica1, Lilia Matei1, Laura Denisa Dragu1, Cristian Coman2,
Mihaela Economescu-Chivu1, Irina Alexiu1, Laura Georgiana Necula1, Cristina Mambet1,
Ana Neagu1, Saviana Nedeianu1, Carmen C. Diaconu1, Iuliana Crisan3, Coralia Bleotu1
1
Inst. Virusologie „Ștefan S. Nicolau”, București; 2INCDMM „Cantacuzino”, București;
3
S.C. HOFIGAL Export Import S.A., București
Materiale compozite pe bază de nanoparticule anorganice și colagen destinate tratamentului
rănilor
Denisa L. Dragu1, Lilia Matei1, Sabina Zurac3, Ionela Andreea Neacsu2, Anton Ficai2, Ana I. Neagu1,
Mihaela Chivu-Economescu1, Bianca Tihuan4, Ecaterina Andronescu2, Carmen Cristina Diaconu1,
Coralia Bleotu1
1
Inst. Virusologie „Ștefan S. Nicolau”, București; 2Facultatea de Chimie Aplicată și Știința Materialelor,
Universitatea Politehnica, București; 3UMF „Carol Davila”, București; 4SANIMED, Călărași
Efectele biologice induse de tratamente cu medicamente asupra proliferării pe celulele de
cancer de sân MCF-7
Mirela A. Mihăilă, Camelia Mia Hotnog, Marinela Bostan, Viviana Roman, Ion Gabriela, Lorelei Irina
Brașoveanu
Inst. Virusologie „Ștefan S. Nicolau”, Centrul de Imunologie, București
Modularea unor markeri angiogenici în linii tumorale de colon cu status mutațional diferit al
P53
Camelia Mia Hotnog, Mirela Mihăilă, Marinela Bostan, Lorelei Irina Brașoveanu
Inst. Virusologie „Ștefan S. Nicolau”, Centrul de Imunologie, București
Astro-imunologie: Profilul de expresie genică în celule monocitare umane expuse la radiație

relevantă pentru spațiul cosmic
Gina Manda1, Ionela Neagoe1, Maria Dobre1, Elena Milanesi1, Ulrich Weber2, Nicole Averbeck2
1
INCD „Victor Babeș”, București; 2GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany
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Markeri de celule stem corelați cu nivelul de factori angiogenici și citokine în glioame

Maria Linda Popa1,2, Adrian Claudiu Popa3, Ana-Maria Enciu1,2, Ionela Daniela Popescu1,
Elena Codrici1, Simona Mihai1, Laura Necula1,4, Lucian Albulescu1, Cristiana Tanase1,5
1
INCD „Victor Babeș”, București; 2UMF „Carol Davila”, București; 3Centrul de Cercetări Științifice
Medico-Militare, București; 4Inst. Virusologie „Ștefan S. Nicolau”, București;
5
Universitatea „Titu Maiorescu”, Inst. Cajal, București
Modularea răspunsului inflamator prin integrarea materialelor bioactive la nivelul pulpei

dentare
Khaled Al Ghieb1, Mihaela Itul Toderesc1, Bianca Galaţeanu2, Octav Ginghină3, Carolina Negrei1
1
Disciplina Toxicologie, Facultatea de Farmacie, UMF „Carol Davila”, Bucureşti; 2Facultatea de Biologie,
Universitatea Bucureşti; 3Disciplina Chirurgie şi Anestezie Generală, Facultatea de Medicină Dentară,
UMF „Carol Davila”, Bucureşti
Evaluarea proliferării, citotoxicității și a efectelor apoptotice induse de nanoparticule

Elena Codrici1, Alexandra Cătălina Vîlceanu2, Ionela Daniela Popescu1, Simona Mihai1,
Ana-Maria Enciu1,2, Lucian Albulescu1, Radu Albulescu1,3, Codorean Eleonora1, Mircea Leabu1,
Butu Alina4, Cristina Mihaela Luntraru5, Cristiana Tanase1,3
1
INCD „Victor Babeș”, București; 2UMF „Carol Davila”, București; 3Universitatea „Titu Maiorescu”,
București; 4INCD pentru Științe Biologice, București; 5Hofigal Export-Import SA, București
Uleiul de cătină protejează doar parțial și temporar celulele epidermale displazice de iradierea
cu UV-A
Dudău Maria1, Alexandra Catalina Vilceanu2, Ana-Maria Enciu1,2, Elena Codrici1, Simona Mihai1,
Ionela Daniela Popescu1, Lucian Albulescu1, Isabela Tarcomnicu3, Cristiana Pistol Tanase1,4
1
INCD „Victor Babeș”, București; 2UMF „Carol Davila”, București; 3SC Cromatec Plus SRL, București;
4
Universitatea „Titu Maiorescu”, București
Leziunile musculare și strategie non-invazivă pentru regenerarea țesutului

Gisela Găină1,2, Emilia Manole1,3
1
INCD „Victor Babeș”, București; 2Facultatea de Biologie, Universitatea din București;
3
Spitalul Clinic Colentina, București
O nouă metodă de extracție a antigenelor de melanom din specimene histopatologice fixate

în formol și împarafinate
Teodora Grigore1, Adina Dobre1, Anca Filimon1, Sabina Zurac2, Gabriela Negroiu1
1
Inst. de Biochimie al Academiei Române, București; 2Spitalul Clinic Colentina, București
Importanța diagnosticului imunologic pentru pacienții cu toxocarioza și simptome alergice

Patricia Mihăilescu1,2, Carmen-Michaela Crețu1,3, Claudia Istrate1
1
Eco-Para-Diagnostic SRL, București, România, 2Universitatea București, Facultatea de Biologie;
3
UMF „Carol Davila”, Departament Parazitologie
Modele inflamatorii în evaluarea bolii renale cronice

Simona Mihai1, Elena Codrici1, Ionela D. Popescu1, Ana-Maria Enciu1,2, Lucian Albulescu1,
Cristina Mihaela Luntraru3, Gabriela Anton4, Cristiana Tanase1,5
1
INCD „Victor Babeș”, București; 2UMF „Carol Davila”, București; 3Hofigal Export-Import SA, București,
România; 4Inst. Virusologie „Ștefan S. Nicolau”, București; 5Universitatea „Titu Maiorescu”, Inst. Cajal,
București
Evaluarea biocompatibilității și a proprietăților regenerative ale biomaterialelor pe bază de

colagen
Ionela Daniela Popescu1, Elena Codrici1, Simona Mihai1, Ana-Maria Enciu1,2, Lucian Albulescu1,
Radu Albulescu1, Mihaela - Adi Lupu3, Cristiana Tanase1,4
1
INCD „Victor Babeș”, București; 2UMF „Carol Davila”, București; 3SC Sanimed International Impex SRL;
4
Universitatea „Titu Maiorescu”, București

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JOI, 19.09.2019
09.00–10.30 Workshop: „Imunologia transplantului – o continuă provocare”

Moderator: Prof. Univ. Dr. Ileana Constantinescu, Centrul de Imunogenetică și Virusologie,
Inst. Clinic Fundeni, UMF „Carol Davila”, București
Co-moderator: Conf. Univ. Dr. Daniel Boda, UMF „Carol Davila”, București,
Președinte Asociația de Imuno-Dermatologie
Impactul potrivirii alelice HLA în supraviețuirea de lungă durată a pacienților cu transplant de

celule stem hematopoietice
Dr. Larisa Denisa Vişan¹,², Ana Moise¹,², Adela Maria Toader¹, Corina Andreea Rotărescu¹,²,
Mirela Maria Iacob¹, Ion Mărunţelu¹,², Andreea Mirela Caragea¹,², Adriana Tălăngescu¹, Ileana
Constantinescu¹,²
1
Centrul de Imunogenetică și Virusologie, Institutul Clinic Fundeni, București;
2
UMF „Carol Davila”, București
Dinamica monitorizării alogrefarii la pacienți cu transplant medular prin chimerism, dozarea

tratamentului imunosupresor și managementul infecțiilor virale posttransplant
Dr. Corina Andreea Rotărescu1,2, Ana Moise1,2, Larisa Denisa Vişan1,2, Ion Mărunţelu1,2,
Andreea Mirela Caragea1,2, Mirela Maria Iacob1, Adriana Tălăngescu1, Ileana Constantinescu1,2
1
2
Abordarea tehnologiei de înaltă rezoluție (NGS) în tiparea alelica HLA - importantă în găsirea
unui donator de celule stem neînrudit compatibil
Prof. Univ. Dr. Ileana Constantinescu¹,², Ana Moise¹,², Larisa Denisa Vişan¹,², Ion Mărunţelu¹,²,
Adriana Tălăngescu¹, Mirela Maria Iacob¹, Corina Andreea Rotărescu¹,², Andreea Mirela Caragea¹,²,
Marina Manea¹,³
1
Centrul de Imunogenetică și Virusologie, Institutul Clinic Fundeni, București; 2UMF „Carol Davila”,
București; 3Lab. Analize Medicale, Institutul Clinic Fundeni, București
Aspecte ale imunologiei pediatrice în abordarea procedurii de transplant la copil

Dr. Andreea Mirela Caragea¹,², Adriana Tălăngescu¹, Ana Moise¹,², Larisa Denisa Vişan¹,²,
Mirela Maria Iacob¹, Ion Mărunţelu¹,², Corina Andreea Rotărescu¹,², Ileana Constantinescu¹,²
1
2
Aspecte ale polimorfismului alelic HLA la pacienți cu insuficiență renală cronică care
urmează să efectueze un transplant renal
Dr. Ion Mărunțelu1,2, Daniela Filofteia Nedelcu1, Ana Moise1,2, Adela Maria Toader1,
Larisa Denisa Visan1,2, Corina Andreea Rotarescu1,2, Mirela Maria Iacob1, Adriana Talangescu1,
Ileana Constantinescu1,2
1
2

Moderator: Prof. Univ. Dr. Monica Neagu, INCD „Victor Babeș”, București; Facultatea de Biologie,
Characterization of Donor-Specific Alloreactive CD4+ and CD8+ Cellular Immune T Cell

Responses in the Lung Allograft and Blood in Lung Transplant Recipients
Prof. Univ. Dr. Iulia Popescu
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of
Pittsburgh School of Medicine, Pittsburgh, USA

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11.00-11.15 Pauză

Moderator: Conf. Univ. Dr. Daniel Boda, UMF „Carol Davila”, București;
Psoriazisul vulgar pediatric – what’s new?

Prof. Univ. Dr. Daciana Brănişteanu1, Cătălina Ioana Branișteanu1, Andreea Dimitriu²
1
Universitatea de Medicină și Farmacie “Grigore T. Popa”, Iași;
²Arcadia- Spitale și Centre Medicale, Iași
11.45-13.15 Prezentări orale

Moderator: Prof. Univ. Dr. Daciana Brănişteanu, UMF „Grigore T. Popa” Iaşi
Infecția HPV. Key messages

Conf. Univ. Dr. Daniel Boda
UMF „Carol Davila”, București; Președinte Asociația de Imuno-Dermatologie
Prea frumos ca să fie adevărat… și totuși…

Conf. Univ. Dr. Patricia Cristodor
UMF „Victor Babeș”, Timișoara
Simpozion Cedraflon: „Bucuria fiecărui pas”

Prof. Univ. Dr. Daciana Brănişteanu
UMF „Grigore T. Popa” Iaşi
Durerea – Principii manageriale

Șef Lucrări Dr. Nicuța Manolache
Universitatea “Dunărea de Jos”, Galaţi
Simpozion Detralex: „Atenție la neatenție”


Moderatori: Prof. Aristides Tsatsakis, Director al Departamentului de Toxicologie și Medicină
Legală, Facultatea de Medicină, Universitatea din Creta, Heraklion &
Conf. Univ. Dr. Daniel Boda, UMF „Carol Davila”, București;
Metabolism and immune-metabolism

Prof. Dr. med. H. Joachim Seitz, Dir (em.)
Institute Biochem. Endocrinology, University Medical Center Hamburg-Eppendorf
HIV-1 and HLA-C: a matter of stability

Prof. Univ. Dr. Donato Zipeto
Department Neuroscience, Biomedicine and Movement Science, School of Medicine, University of
Verona, Italy
Current advances on Telomeres research

Prof. Aristides Tsatsakis
Director al Departamentului de Toxicologie și Medicină Legală, Facultatea de Medicină, Universitatea
din Creta, Heraklion

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16.00-16.15 Pauză
16.15–17.00 Prezentări orale

Moderatori: Conf. Univ. Dr. Patricia Cristodor, UMF „Victor Babeș”, Timișoara &
Șef Lucrări Dr. Nicuța Manolache, Universitatea „Dunărea de Jos”, Galaţi
La frontierele medicinei: certitudinile și provocările medicinei regenerative

Conf. Univ. Dr. Florian Berghea
UMF „Carol Davila” București
Istoria anticorpilor terapeutici și premiile Nobel

Prof. Univ. Dr. Georgeta Sinițchi
Centrul Medical Alergologic Atopia, Iasi
17.00-17.30 Sedință SIR – Adunarea generală a membrilor SIR pentru alegerea Consiliului Director
VINERI, 20.09.2019: „Imuno-dermato-pediatria la granița colaborării

între pediatri, imunologi, dermatologi și alergologi”
Conferință comună a Asociației Române de Imuno-Dermatologie,

a Societății de Imunologie din România, a Societății Române de Alergologie
și Imunologie Clinică și a Societății Române de Pediatrie

Moderator: Prof. Univ. Dr. Georgeta Sinițchi,
Importanța imunofenotipării în diagnosticul și monitorizarea terapiei în leucemiile acute

limfoblastice la copil
Conf. Univ. Dr. Anca Coliță
09.30–10.30 Prezentări orale

Moderatori: Prof. Univ. Dr. Carmen Bunu Panaitescu, UMF Timișoara &
Prof. Univ. Dr. Victor Cristea, UMF „Iuliu Hațieganu”, Cluj-Napoca, Președinte
Societatea de Imunologie din România
Tehnici de regenerare cutanată

Șef Lucrări Dr. Gabriela Stoleriu
Universitatea „Dunărea de Jos”, Galați
PCR based multiplex detection of most important dermatophytes

Dr. Markus Cavalar
Șef secție de diagnosticare infecțioasă moleculară, EUROIMMUN Medizinische Labordiagnostika AG
Medicina personalizată în cabinetul medicului de familie

Dr. Adriana Mihălaș
Centrul Medical de Diagnostic, Tratament Ambulator și Medicină Preventivă, București

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Microbiomul cutanat și dermatita atopică la copil

Prof. Univ. Dr. Georgeta Sinițchi
10.30-10.45 Pauză

Moderatori: Prof. Univ. Dr. Carmen Bunu Panaitescu, UMF Timișoara &
Șef Lucrări Dr. Vlad Voiculescu, UMF „Carol Davila”, București
Noi perspective ale terapiei biologice la astm în copilărie

Prof. Univ. Dr. Carmen Bunu Panaitescu
UMF Timișoara
Probioticele - profilaxie și tratament în dermatita atopică

Prof. Univ. Dr. Diana Deleanu
UMF „Iuliu Hațieganu” Cluj-Napoca
Imunodeficiențele primare: epidemiologie, tablou clinic și detecție precoce

Asist. Univ. Dr. Irena Nedelea
Sensibilizarea raportată la fenotipurile dermatitei atopice

Dr. Carina Petricău
Institutul Regional de Gastroenterologie și Hepatologie Cluj-Napoca
Rolul polimorfismelor receptorului vitaminei D în melanom și carcinoamele cutanate

Șef Lucrări Dr. Simona Corina Șenilă
UMF„Iuliu Hațieganu”, Cluj-Napoca
Rolul biofilmului bacterian în afecțiuni dermatologice

Prof. Univ. Dr. Mircea Ioan Popa
Corelații clinice și imunologice în alergia la proteina din laptele de vacă

Prof. Univ. Dr. Coriolan Emil Ulmeanu¹, Viorela Gabriela Nițescu²
¹UMF „Carol Davila” București; ²SCUC „Grigore Alexandrescu”, București
Mastocitoza la copil. Aspecte evolutive și terapeutice

Șef Lucrări Dr. Elena Camelia Berghea
Managementul bolii venoase cronice a piciorului

Dr. Gabriel Ianoși
UMF Craiova

Moderatori: Dr. Gheorghița Isvoranu, INCD „Victor Babeș”, București &
Dr. Cornel Ursaciuc, Vice-Președinte Societatea de Imunologie din România, București
Citokine și molecule de adeziune celulară implicate în patologia umană (experiență

personală)
Prof. Univ. Dr. Victor Cristea
UMF „Iuliu Hațieganu”, Cluj-Napoca; Președinte Societatea de Imunologie din România

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14.30-14.45 Simpozion Sanofi Genzyme
Dupilumab: un nou standard în tratamentul dermatitei atopice moderate și severe

14.45–16.00 Simpozion: „Exanteme maculo-papuloase post-medicamentoase”

Moderatori: Conf. Univ. Dr. Roxana Silvia Bumbăcea, Președinte Societatea Română de Alegologie
şi Imunologie Clinică; Șef Disciplină Alergologie, UMF „Carol Davila”, București; Sp. Clinic
de Nefrologie „Dr. Carol Davila”, București &
Șef Lucrări Dr. Elena Camelia Berghea, UMF „Carol Davila”, București
Exantemele virale versus exantemele post medicamentoase

Asist. Univ. Dr. Selda Ali
Spitalul Clinic de Nefrologie “Dr. Carol Davila”, București
Particularități ale exantemelor maculo-papuloase la copii

Evaluarea alergologică a exantemelor maculo-papuloase

Conf. Univ. Dr. Roxana Silvia Bumbăcea
Președinte Societatea Română de Alegologie şi Imunologie Clinică (SRAIC); Șef Disciplină Alergologie,
UMF „Carol Davila”, București; Spitalul Clinic de Nefrologie „Dr. Carol Davila”, București
16.00-16.15 Pauză

Moderatori: Dr. Simona Ianoși, UMF Craiova &
CSI Dr. Mihail Alecu, Sp. Clinic de Boli Infecțioase și Tropicale „Dr. Victor Babeș”,
București
Toll like receptor în patogenia psoriazisului

CSI Dr. Mihail Alecu
Spitalul Clinic de Boli Infecțioase și Tropicale „Dr. Victor Babeș”, București
Pityriazis rubra pilar paraneoplazică (PRP): prezentare de caz și revizuirea literaturii

Șef Lucrări Dr. Laszlo Fekete
UMF Târgu Mureș
Laserul excimer în tratamentul psoriazisului – prezentare de caz și review al literaturii

Dr. Alin Tatu/Dr. Florin Bujoreanu
Universitatea Dunărea de Jos, Galați
Psoriazisul - date noi despre epidemiologie și factori de risc

Dr. Simona Ianoși
UMF Craiova
Noi tendințe în cercetarea dermatologică - metode alternative non-animale

Prof. Univ. Dr. Farm. Cristina Dehelean
Facultatea de Farmacie, Universitatea de Medicină şi Farmacie „Victor Babeş”, Timişoara

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SÂMBĂTĂ, 21.09.2019: „Imuno – dermato – oncologie”
09.00–12.30 Workshop: „Imunodiagnosticul și imunoterapia melanomului și altor tumori cutanate”

Organizat în cadrul Proiectului PN-III-P1-1.2-PCCDI-2017-0341 PATHDERM
Moderatori: Prof. Univ. Dr. Sabina Zurac, Sp. Clinic Colentina, București &
Prof. Univ. Dr. Monica Neagu, INCD „Victor Babeș”, București; Facultatea de Biologie,
Epithelial-mesenchymal transition peculiarities in melanocytic nevi with tumor vascular

protrusion
Oana Stefan1, Georgiana-Irina Tudor1, Corina Constantinescu1, Cristina Luca1, Daniel Boda2,
Constantin Caruntu2, Virginia Chitu1,2, Cristiana Popp1, Alexandra Cioroianu1,2, Mirela Cioplea1,
Luciana Nichita1,2, Sabina Zurac1,2
1
Sp. Clinic Colentina, București; 2UMF „Carol Davila”, Bucureşti
Dopachrometautomeraza este un nou reglator al căilor de stres în melanom

Dr. Anca Filimon, Teodora Grigore, Adina Dobre, Gabriela Negroiu
Departamentul de Biologie Moleculară a Celulei, Institutul de Biochimie al Academiei Române,
București, România
Asocierea dintre dermatomiozită și bolile maligne

CSI Dr. Emilia Manole1,2, Gisela Găină1,3, Alexandra Bastian4,5
1
INCD „Victor Babeș”, București; 2Centrul de Cercetare – Departament Patologie, Sp. Clinic Colentina,
București; 3Departament Biochimie și Biologie Moleculară, Facultatea de Biologie, Universitatea din
București; 4UMF „Carol Davila”, București; 5Departament Patologie, Sp. Clinic Colentina, București
Calea de semnalizare Wnt 5a în patologia dermatologică

Prof. Univ. Dr. Robert Ancuceanu
Biopsia virtuală in vivo a cancerului cutanat

Conf. Univ. Dr. Constantin Căruntu
Melanomul malign coroidian în secolul XXI – opțiuni și limite în practica de zi cu zi

Șef Lucrări Dr. Horia Tudor Stanca
Rolul ARN-urilor noncodificatoare în patologia tumorală. Oportunități terapeutice

Prof. Univ. Dr. Ioana Berindan
UMF „Iuliu Hațieganu” Cluj Napoca
Particulritățile tranziției epitelial-mezenchimale în melanomul cutanat

Asist. Univ. Dr. Gabriela Turcu
Particularitățile tranziției epitelial mezenchimale în epitelioamele cutanate spinocelulare

Asist. Univ. Dr. Roxana Nedelcu

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ABSTRACTE
MIERCURI, 18 SEPTEMBRIE 2019

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RARE DISEASES OF THE ADULT

- STATE OF HEALTH OF PATIENTS WITH CVID
Victor Cristea, Nicolae Miron (Sweden),

Livia Ona (Germany), Assist. Univ. Irene Nedelea,
For a long time, the problem of primary immunodeficiencies was discussed

only in the pediatric departments, the doctors being, for the most part, giving
the impression that this type of disease only appears in children who usually do
not survive more than 3-4 years.
The development of molecular biology techniques, the conduct of
randomized studies and especially the initiation of effective therapies has
fundamentally changed the thinking of specialists. The survival rate, but also
the quality of life of those affected by such “rare diseases” began to increase
significantly. Clinical observations of the past decades have shown that a
significant proportion of those with immune deficiencies lead a relatively
normal life without obvious symptomatology until the 5-6 decades of life. The
new classifications - discouraging in their complexity, at least for practicing
physicians, speak of a series of manifestations of primary immunodeficiencies
that have sometimes been identified only in 2-3 persons. In addition, there
are more and more cases in which those with such disorders have added
manifestations of hypersensitivity, autoimmune diseases or neoplasms. In some
situations, even cases occur in which the disease occurs within the family.
However, regardless of the associated diseases at least so far, the major
role of substitution therapy for maintaining quasi-normality parameters of the
patient’s life is clear.

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EARLY KLRG1+ BUT NOT CD57+CD8+ T CELLS

IN PRIMARY CMV INFECTION PREDICT
EFFECTOR FUNCTION AND VIRAL CONTROL
Iulia D. Popescu1, Aki Hoji1, Mathew R. Pipeling1, Pali D. Shah2,

Spencer A. Winters1, and John F. McDyer1
1
Division of Pulmonary, Allergy, and Critical Care Medicine,
Department of Medicine, University of Pittsburgh School of
Medicine, Pittsburgh, Pennsylvania, 15213, USA;
2
Division of Pulmonary and Critical Care Medicine, Department
of Medicine, Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA.
CMV remains an important opportunistic pathogen in high-risk lung

transplant recipients (LTRs). We characterized the phenotype and function of
CD8+ T cells from acute/primary into chronic CMV infection in 23 (donor+/
recipient-; D+R-) LTRs and found rapid induction of both KLRG1+ and/or CD57+
CMV-specific CD8+ T cells with unexpected co-expression of CD27. These
cells demonstrated maturation from an acute effector (TAEFF) to an effector
memory (TEM) phenotype with progressive enrichment of KLRG1+CD57+CD27-
cells into memory. CMV-specific KLRG1+ TAEFF cells were capable of in vitro
proliferation that diminished upon acquisition of CD57, whereas only KLRG1+
expression correlated with T-bet expression and effector function. In contrast
to blood TAEFF cells, lung mucosal TAEFF cells demonstrated reduced KLRG1/T-
bet expression but similar CD57 levels. Additionally, increased KLRG1+TAEFF cells
were associated with early immune viral control following primary infection.
Together, our findings provide new insights into the roles of KLRG1 and CD57
expression in human T cells, forming the basis for a refined model of CD8+ T cell
differentiation during CMV infection.
We report novel CMV-specific KLRG1+CD27+CD57+/− CD8+ TAEFF in primary
infection. KLRG1+ TAEFF correlate with function and control of CMV in lung
transplant patients.

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IMMUNE PATTERN
IN CUTANEOUS MELANOMA
Monica Neagu1,2,3, Carolina Constantin1,3, Constantin Caruntu4,

Mihaela Surcel1,2, Sabina Zurac3,4
1
“Victor Babeș” National Institute of Pathology, Immunology Department,
99-101 Spl Independentei, Bucharest; 2Faculty of Biology, University of
Bucharest, 93-95 Splaiul Independentei, Bucharest; 3Colentina University
Hospital, Pathology Department, 19-21 Stefan cel Mare Blv., Bucharest;
4
“Carol Davila” University of Medicine and Pharmacy, 8 Eroii Sanitari Blv,
Bucharest.
With the advent of the new era of immune-therapy, new rapidly emerging
aspects are highlighted from both fundamental research and clinical applications.
In this light several proteomic/genomic biomarkers in patients diagnosed with
cutaneous melanoma are to be evaluated.
Several proteomic technologies were used to identify and quantify biomarkers
from patients sera: multiplex, protein microarray, mass-spectrometry. Genomic
technologies such as CGH-array was used to identify copy number variation in
genetic material extracted from tumors. We have shown that peripheral immune
cells have a particular pattern in melanoma, whether in patients or in mouse
experimental models. A Th1-type immune signature is associated with good
prognosis. Another finding reported by us is that inflammation markers govern
the prognosis and using multiplexing technology we have obtained in this pattern
IL-6 as key player as prognostic factor. Another player is the chemokine IL-8 that is
increased in advanced stages. Tumors are highly heterogeneous in terms of protein
and gene expression. Using CGH-array technology we have shown differences in
the same tumors in terms of CNV. Using protein microarray technology we have
shown that several proteins are over-expressed in the sera of melanoma patients.
Out of all these, leptin, a hormone appending mainly to the adipose tissue was
found increased 10-30 times in comparison to normal serum. Aplying STRING
programm we have shown that leptin, among others, is an inducer of IL-6.
As the recently developing immuno-therapy is more efficient in combination, so
the biomarkers that should monitor therapy, should also be used in combination.
Acknowledgement. PN-III-P1-1.2-PCCDI-2017-0341/2018, PN 19.29.01.01,
EPITRAN COST ACTION 16120/2018.
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THE ROLE OF LANGERHANS CELLS

IN DERMATOLOGY
Manole Cojocaru,
“Titu Maiorescu” University, Faculty of Medicine,

Bucharest, Romania
The skin is an integral part of immune system, it contains cellular elements

which are needed for the initiation and expression of immune response.
Langerhans cells (LCs) are dendritic cells originating in the bone marrow.
LCs are epidermal antigen presenting cells which play a crucial role in
allergic contact hypersensitivity, viral diseases, graft versus host disease and
elimination of neoplastic cell clones. They express antigens conjugated with
major histocompatibility complex (MHC) class II positive molecules on their
surfaces for presentation to T-helper lymphocytes. LCs cannot be identified
in routinely prepared histologic testing but can be visualised at the light
microscope level by histochemical and immunologic techniques. Appropriate
methods for the detection of LCs in dermatology are histoenzymatic
methods of adeno sintriphosphatase (ATP-ase), acid phosphatase (AP),
alpha-naphthylacetatesterase (ANAE) and peroxidase-antiperoxidase
immunohistochemistry method with polyclonal S-100 protein antibody (PAP).
LCs are the only cells in normal skin with ATP-ase activity. Histoenzymatic
methods used in patients with atopic dermatitis, vitiligo, mycosis fungoides,
Behçet’s disease, lichen ruber planus, psoriasis vulgaris, irritant dermatitis and
allergic contact dermatitis demonstrated LCs in epidermis and dermis. ANAE
and AP showed concordance and were suitable histochemical markers for
LCs distribution and macrophages in the dermis in mycosis fungoides, atopic
dermatitis, psoriasis vulgaris, irritant chronic dermatitis and Behçet’s disease.
Studies of the human skin showed a strong activity of calcium-activated
adenosine triphosphatase in LCs. Immunohistochemical methods define the
role of LCs in dermatology more precisely and allow complete immunologic
recognition within the epidermis.
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HLA HAPLOTYPES AND LINKAGE

DISEQUILIBRIUMS IN NORTH-EASTERN
ROMANIA AND EUROPE
Mariana Pavel-Tănasă1, Corina Cianga1,2, Daniela Constantinescu1,2,

Camelia Mihaila2, Petru Cianga1,2
1
Department of Immunology, “Grigore T. Popa”
University of Medicine and Pharmacy of Iasi, Romania;
2
Laboratory of Immunology, “St. Spiridon” Hospital, Iasi, Romania.
The human leukocyte antigen (HLA) represents a large group of genes

encoding for the highly polymorphic major histocompatibility complex (MHC)
proteins in humans. The human MHC maps to the short arm of chromosome 6
(6p21) and is divided in three distinctive regions, correspondent to three classes
of molecules. Hence, a remarkable number of allelic variants were characterized
so far. As these genes are closely linked, they are inherited in set, as an HLA
haplotype. This type of inheritence tends to favour certain combinations of HLA
alles, referred as linkage disequilibriums.
Two HLA I genes (A, B) and one HLA-II gene (DRB1) were routinely
investigated by PCR amplification, or by PCR and hybridization. A number of
1046 family members were considered and a number of 1892 haplotypes could
be thus identified. SPSS Statistics (version 25) led to the characterization of 487
distinctive haplotypes and to the identification of a set of linkage disequilibriums.
The results were further compared with the HLA allele frequencies described for
the population of Romania and, respectively, for the population of Moldova.
This is the first study performed in Romania aimed to identify both the most
frequent HLA haplotypes as well as the linkage disequilibriums. The data are
of outmost importance as the HLA compatibility between the donor and the
recipient is critical for the kidney and bone marrow transplant.

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MODULATION OF IMMUNE RESPONSE

IN DIABETES MELLITUS
Manuela Ciocoiu1, Magda Badescu1, Daniela Jitaru2,

Iris Bararu-Bojan1, Maria Cristina Vladeanu1, Codruta Badescu3
1
Department of Pathophysiology, UMF “Grigore T. Popa” Iasi, Romania;
2
Regional Institute of Oncology Iasi, Romania;
3
Department of Internal Medicine I, UMF “Grigore T. Popa” Iasi, Romania.
The inflammatory immune response of the islets of Langerhans is known to

represent the pathogenetic stage of type 1 diabetes mellitus and to materialize in
the insulitis process. The monocytes/macrophages and activated T lymphocytes
are the cells infiltrating the islets. It is known that the immunological markers,
including anti-islet cytoplasmic antibodies, antiinsulin antibodies, and many
others, may be detected in the serum. Streptozotocin-induced diabetes in
Wistar rats can be considered a good experimental model for the study of the
insulin-dependent diabetes mellitus. In this study, we have observed the role of
the natural antioxidants such as those from Aronia melanocarpa and Sambucus
nigra in the recovery of the immune system in white males Wistar rats with
streptozotocin-induced diabetes. The evaluation of the immune phenotype was
undertaken by the help of flow cytometry in diabetic rats, with or without the
administration of an extract of Aronia melanocarpa and Sambucus nigra, rich in
polyphenols. The quantitative and functional phenotypic analysis of the immune
cells before andafter the appearance of the diabetes in Wistar rats protected by
polyphenols administration highlighted the presence of a significant increase
in the number of the T helper lymphocytes, as well the production of T naive
lymphocytes, respectively a decrease in the population of T CD4+CD45RC+
cells with memoryin comparison to the group of diabetic rats.
All these results prove that the immune defense in diabetes mellitus in the
animal experimental model can be significantly improved by the administration
of natural polyphenols.

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IN VITRO STUDY OF THE EFFECT

INDUCED BY MnCI2
Ștefania Lascăr1, Irina Elena Ionescu1, Raluca Elena Lăzărescu1,

Vlad Tofan1, Mihaela Diaconu1,2, Cătălin Țucureanu1, Ana Șerbănescu1,
1
“Cantacuzino” National Military-Medical Institute for Research
and Development, Bucharest, Romania;
2
University of Bucharest, Faculty of Biology, Bucharest, Romania;
3
“Titu Maiorescu” University, Faculty of Pharmacy, Bucharest, Romania.
Manganese (Mn) is one of the most abundant metal in natural environments

and is an essential microelement for the living organisms, at low dose. However,
at higher concentration, manganese accumulates in various body parts and can
interfere with metabolic processes.
The objective of the present study was to investigate the effect of manganese
on human immune cells. The human leukemia monocytic cell line THP-1 was
cultured in RPMI 1640 medium supplemented with 10% FBS, antibiotics, and
2 L-glutamine. Acute exposure of THP-1 cell to manganese was tested using
61mM - 0,037mM MnCl2 solutions. After 2h of treatment the viability test was
performed by fluorescent microscopy using acridine orange (AO) and propidium
iodide (IP) dye. The efect of cronic treatment was evaluated by exposing THP-
1 cells for 1-5 days to MnCl2 in increasing concentrations (0.0001mM –1mM).
The cytotoxic effect was studied by Trypan Blue assay and Annexin V FITC/PI,
CFSE assays. The results obtained after short term exposure of cells indicated
that the cytotoxicity range was from 0.3mM to 15mM. After chronic exposure
of cells to different manganese concentrations, one can notice a decrease in
cell viability in conditions of at least 3 times lower concentrations (0.1mM and
1mM) than after short term exposure. Our results indicated that both acute and
chronic exposure of cells to Mn salt lead to decrease in cell viability/proliferation
although in different concentration range.
This work is supported by the Ministry of Research and Innovation, project
number PN-III-P1-1.2-PCCDI-2017-0737 (ARTEMIS).

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PRO-AND ANTITUMOR ROLE

OF INTERLEUKINS 1 TO 41
Ovidiu Farc¹, Victor Cristea²
¹Immunology Department of “Iuliu Hatieganu” Cluj-Napoca, Romania;

²Immunology Department of “Iuliu Hatieganu” Cluj-Napoca, Romania.
Introduction: The present work is a review of the current knowledge about

the 41 known interleukins and their intervention in cancer.
Methods: We conducted a search through Pubmed, using ìnterleukin no`
and `cancer` as key words. We selected 400 articles, originals and reviews,
and kept the most recent, from 2006. (250 articles). We evaluated the pro-or
antitumoral action of each molecule.
Results: The proinflammatory interleukins (IL1,6, TNFα,20,32,36,41). Most
of them areproangiogenic, pro-invasive in tumors. Their inhibition is therefore
considered. They also support antitumor defense.
The interleukins stimulatory for the lymphocytes are IL 2,9.12,7,15,21.27
and interferons. They support the antitumor defense and therefore they are
used in therapy (IL2, IFN) or are in different stages of clinical evaluation. The
Th2 cytokines-ILs 4,5,13,19,24,25,31,33.39, most of them being protumoral and
proinvasive, with the exception of IL 24and IL 25, are by consequence seen as
possible targets
Th17 cytokines (IL 23,17,22,26) are proangiogenic and favor tumor growth.
They are considered for inhibition.
Antiinflammatory interleukins - ILs 10 and TGF are pro-tumoral, depressing
the antitumor immunity, while IL 35 and 37 are tumoricideonthe tumor cells.
Conclusions: The cytokines in tumors act in complex networks. We end our
study by offering a model for their action on the tumor cells and on the tumor
environment, through which we try both to describe the complex relations within
tumors, and to offer a tool to improve strategies of therapeutical approaches
in tumors.
Keywords: interleukins, cancer

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A DOGMA CHANGE IN IMMUNOLOGY
Corina Cianga1,2, Petru Cianga1,2

1
Department of Immunology, University of Medicine
and Pharmacy “Grigore T. Popa”, Iași
2
Laboratory of Immunology, “St. Spiridon” Hospital, Iasi, Romania
The Immune System is characterized by a huge level of ambiguity. There

is an enormous diversity of the antigen receptors specificity, generating
“immune repertoires” that lead to an “immune identity” which customizes
the immune response of each individual. The first level of ambiguity is to be
found in the ontogeny of the B and T cells, as many unnecessary or unwanted
lymphocytes are generated. Furthermore, the high level of ambiguity of the
peripheral immune responses has led to the hypothesis that the main role of
the Immune System is to make a distinction between the dangerous infections
and the non-dangerous infections. The key issue and thus the main challenge
is to understand how and if this ambiguous behavior of the Immune System is
advantageous, or even necessary.

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IMMUNOLOGIC INVOLVEMENT OF CELIAC

DISEASE IN THE PATHOGENY OF ISCHEMIC
STROKE AND OF PERIPHERAL NEUROPATHY
Inimioara Mihaela Cojocaru1,2
1
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania;
2
Department of Neurology, Colentina Clinical Hospital,
Bucharest, Romania.
Celiac disease is an immune-mediated enteropathy attributed to a reaction

to gliadin, a protein fraction contained in some grains. A 56-year-old man
presented acute right hemiparesis and aphasia. The physical examination was
normal. The neurologic examination emphasized right homonimous hemianopsia,
right central facial palsy, deep tendon reflexes abolished, predominant brachial
right hemiparesis, Babinskiꞌs sign on the right side, upper right limb superficial
hypoesthesia, mixed aphasia, predominant expressive. The cerebral CT scan showed
left temporo-parietal hypodensities. Cardiac and supra-aortic trunks examinations
were normal. Serologic investigations showed reduced values of vitamin B12, of
folic acid and high values of homocystein. Electroneurography presented axonal
lenght dependent sensorimotor peripheral neuropathy aspect. Esogastroduodenal
fibroscopy and fundic biopsy showed a suggestive aspect for celiac disease. Anti-
gliadin, anti-endomysial and anti-ganglioside antibodies (anti-GM1 IgM antibodies)
were positive. The diagnosis established were: Celiac disease. Ischemic stroke in
the left superficial middle artery territory. Axonal lenght dependent sensorimotor
peripheral neuropathy. With a gluten-free diet, injectable vitamin B12, folic
acid, antiplatelet therapy the outcome was favorable, with total remission of the
simptomatology in 5 months. Celiac disease should be considered as a potential
etiology of stroke and peripheral neuropathy, both of unknown cause, even in the
absence of gastrointestinal manifestations; it is a tratable cause of these disorders.
Testing of anti-gliadin, of anti-endomysial, of anti-trasglutaminase 2 and of anti-
ganglioside antibodies is essential for the diagnosis.

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EXPRESSION OF B7 IMMUNE CHECKPOINT

RECEPTORS AND LIGANDS IN ACUTE
MYELOID LEUKEMIA
Ion Antohe1,2, Angela Dăscălescu1,2, Cătălin Dănăilă1,2, Amalia Titieanu1,2,

Mihaela Zlei3, Iuliu Ivanov4, Adriana Sireteanu4, Mariana Pavel-Tanasa5,
Petru Cianga5,6
1
Hematology Department, “Grigore T. Popa” University of Medicine and
Pharmacy, Iaşi; 2Hematology Department, Regional Oncology Institute,
Iaşi; 3Immunophenotyping Department, Regional Oncology Institute, Iaşi;
4
Molecular Diagnostic Department, Regional Oncology Institute, Iaşi;
5
Immunology Department, “Grigore T. Popa” University of Medicine and
Pharmacy, Iaşi; 6Laboratory of Immunology, “St. Spiridon” Hospital, Iasi,
Romania.
Helper and cytotoxic T lymphocytes are essential effectors of anti-tumor

immunity in acute myeloid leukemia (AML). The outcome of T cell activation and its
effector function is modulated by a delicate balance of B7 co-stimulatory and co-
inhibitory signals provided by regular antigen presenting cells or AML tumor cells.
We have investigated the expression of B7 checkpoint ligands B7.1, B7.2, PD-L1,
PD-L2, ICOS-L, B7-H3, B7-H4 on AML blasts from 30 newly diagnosed patients, as
well as the expression of their corresponding receptors (CTLA-4, PD-1 and ICOS) on
the bone marrow (BM) T cell maturation populations. We correlated the data with
standard AML prognostic factors.
B7.1 was constantly absent on tumor cells, while B7.2, PD-L1, PD-L2, ICOS-L,
B7-H3 and B7-H4 were expressed isolated or in eight different checkpoint ligand
signatures, including mainly co-inhibitory ligands. B7.2 was the most frequently
expressed B7 molecule. BM CD4+ T cells displayed a central memory phenotype
and constantly expressed high levels of ICOS, while CD8+ T cells predominantly
displayed an effector polarization and expressed higher PD-1. B7 positive patients
expressed slightly higher Treg percentages and higher ICOS and PD-1 levels.
AML with recurrent genetic anomalies did not express B7 ligands and displayed
more frequent naïve T cells, with the exception of NPM1 mutated AML, which was
correlated with B7-H3 expression. AML not otherwise specified (NOS) regularly
displayed B7 molecules and signatures, as well as higher ICOS and PD-1 in B7
positive patients. No correlation was found between the B7 phenotype and ELN
risk subgroups.
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THE PROFILE OF CYTOKINES IN CHRONIC

MARGINAL PERIODONTITIS
Elena Tâlvan, Victor Cristea, Manuela Mihalache
UMF “Iuliu Hațieganu” Cluj-Napoca, Romania
Introduction: The aberrant expression of cytokines or the dysregulation of their

activity has been in various studies associated with the occurrence and development
of a variety of human diseases including periodontal disease. Inflammation from
periodontal disease is initiated and maintained by pro- and anti-inflammatory
cytokines and disruption of the balance between them can cause systemic pro-
inflammatory status, favoring disease progression.
Material and method: The study enrolled 165 subjects who presented at the
Sibiu Oral and Maxillofacial Surgery Clinic in May-September 2015. The clinical and
radiological parameters of the chronic periodontitis were followed. Plasma levels of
the proinflammatory cytokines IL1β, IL6, IL8 and TNF-α and of the anti-inflammatory
interleukins IL4, IL10 and IL13 were analyzed by ELISA immunoassay technique.
Results: Plasma concentration of IL1β, IL6, IL8, and TNF-α was significantly
increased in subjects with periodontal disease. Plasma levels of IL4, IL10 and IL13 were
increased in healthy subjects. There were significant positive correlations between
pro-inflammatory interleukins and significant negative correlations between pro-
and anti-inflammatory interleukins with periodontal disease progression.
Conclusions: Increased levels of pro-inflammatory cytokines IL1b, IL6, IL8
and TNF-a highlight their contribution to the progression of periodontal disease,
causing systemic proinflammatory status. IL4, IL10 and IL13 were correlated with
periodontal health.
Keywords: periodontal disease, cytokines, plasma, ELISA technique

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INTERLEUKINS AS PROGNOSTIC MARKERS IN

COMMUNITY-ACQUIRED PNEUMONIA
Raluca-Elena Tripon¹, Victor Cristea²

¹Infectious Disease department of UMF “Iuliu Hatieganu”
Cluj-Napoca, Romania;
²Immunology department of “Iuliu Hatieganu” Cluj-Napoca, Romania.
Introduction: Community-acquired pneumonia (CAP) remains one of the

major causes of morbidity and mortality worldwide. Pro-inflammatory and anti-
inflammatory interleukins have been studied to elucidate the role that inflammation
plays in its pathogenesis. We aimed to investigateinflammation in CAP, by analyzing
in dynamic, serum levels of eight interleukins (IL) and their predictive value regarding
adverse outcome.
Materials and methods: Forty adult patients with CAP, admitted in the Teaching
Hospital of Infectious Diseases, Cluj-Napoca, Romania from December 2015 to
February 2017, were enrolled in this study. Serum levels of pro-inflammatory: IL-1β,
TNF-α, IL-6, anti-inflammatory: IL-10 and IL-4, along with IL-17A, IL-13 and IL-33
were analyzed in dynamic, on day 1 and day 4. The receiver – operator curves (ROC)
were used to analyze the outcome prediction of IL.
Results: Serum levels of IL-1β, IL-6, TNF-α, but also IL-10 and IL-33 decrease
significantly in dynamic, while IL-4 increases. IL-17A and IL-13 acts like pro-
inflammatory cytokines. We found no correlation between severity scores and
IL. From 40 patients, 9 had adverse outcomes, consists in 9 relapses from which
1 died. IL-6 discriminates alone between adverse and favorable outcome. With
multivariate analysis and multiple regression of all combined IL, we found that there
is a predictive model regarding adverse outcome.
Conclusion: IL-10, IL-17A and IL-33 behave like pro-inflammatory cytokines.
IL-6 is a predictive marker for adverse outcome alone. All IL studied together could
have an impact on adverse outcome.
Keywords: Interleukins, community-acquired pneumonia

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RNA EXPRESSION IN PERIODONTAL DISEASE
Elena Tâlvan, Victor Cristea, Cornelia Braicu, Ioana Berindan Neagoe

UMF “Iuliu Hațieganu”, Cluj-Napoca
Introduction: Diagnostic techniques of periodontal disease have not taken into

account, until recently, the detection of patients with high sensitivity and increased
risk for disease progression. RNAs play a modulatory role of host response to
periodontal pathogen by regulating the secretion of pro-inflammatory cytokines.
Several studies in the field have analized the expression of microRNAs and long
non-coding RNAs in periodontal inflammation seeking to describe a transcriptomic
profile of chronic periodontitis.
Material and method: The study included 65 subjects who were selected from
the Clinic of Oral and Maxillofacial Surgery, Sibiu from September 2017- April
2018. Clinical and radiological parameters of chronic periodontitis were assessed.
Unstimulated saliva was collected and RNA isolation was performed by qRT-PCR
technique.
Results: Salivary expression of long noncoding RNAs GAS5 and H19 was
significantly lower in subjects with periodontal disease compared to the control
group. No significant association between long non coding RNA MALAT1 expression
and periodontal disease was noted. Expression of miR34a and miR155 did not
correlate with the presence of periodontal disease and no statistically significant
differences between the 2 groups were evident. The level of microRNA 146a was
significantly increased in subjects with periodontal disease.
Conclusions: Reduced salivary expression of GAS5 and H19 may be associated
with periodontal disease pathogenesis and miR-146a appears to be a promising
candidate as a biomarker of chronic periodontitis. Saliva is a non-invasive and
accessible biological sample for evaluation of circulating RNAs.
Keywords: periodontal disease, MicroRNA, long noncoding RNA, saliva

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THE INTERLEUKINS 19 AND 33 IN BIOLOGY

AND DISEASE
Ovidiu Farc¹, Victor Cristea²

¹Immunology Department of “Iuliu Hatieganu” Cluj-Napoca, Romania;
²Immunology Department of “Iuliu Hatieganu” Cluj-Napoca, Romania.
Introduction: Interleukins (ILs) are means of connection and cooperation

between the different cells involved in the immune response. Interleukin 19
is a cytokine that targets mainly the skin, whose biology and participation in
inflammation it regulates, and lymphocytes, to whose Th2 differentiation it is
believed to contribute. Interleukin 33 is an alarmin secreted in situations of tissue
destructions, who contributes to the Th2, and under certain conditions, Th1
polarisation and response. In different pathological states, their interventions are
as follows:
- In bronchial asthma, they are increased and contribute to the Th2 inflammation;
in reumathoid arthritis, it contributes to the inflammation; here IL 33 hasa Th1-
stimulating effect; in atherosclerosis they have a protective effect which is Th2
mediated; IL 19 is angiogene; in cancer they both stimulate prolife ration and
invasiveness of tumor cells and the Th2 response, which is mainly protumoral.
- In dermatologic conditions, their action is as follows: In psoriazis, a Th1/17
mediated disease, IL 19 increases, contributing to the inflammation and epidermal
proliferation, while IL33, here, is a Th1/17-inducing cytokine. In atopic dermatitis, in
the acute phase, mediated Th2 and Th22, both cytokines contribute to the process.
In the infections of the skin, IL19 depresses immunity, while in skin cancer, IL33
stimulates the pro tumoral inflammation. The two cytokines are potential targets
in atopic dermatitis astma and cancer; in psoriazis they are not seen as targets in
ischaemia-IL19 could have a good effect.
Conclusion: IL 19 and 33 are less known cytokines, but with a lot of implications
in pathology; their study as biomarkers and targets may be useful.

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PROTEOMICS TOOLS FOR INTEROGATION OF

TRANSDIFFERENTIATION TO BETA CELLS
Radu Albulescu1,2, Daniela Lixandru3, Simona Dima3, Irit Meyvar1, Laura

Georgiana Necula1,4, Cristiana Tănase1,5
1
“Titu Maiorescu” University, Cajal Institute, Bucharest, Romania;
2
National Institute for Chemical Pharmaceutical R&D; 3Fundeni Clinical
Institute; 4“Ștefan S. Nicolau” Institute of Virology;
5
“Victor Babeș” National Institute of Pathology, Bucharest, Romania.
Diabetes mellitus shows increasing prevalence worldwide. βcell function

alteration and loss of βcell characterize both type 1 and type 2 diabetes, with the
onset of cellular loss earlier in type 1 diabetes and in late stage type 2 diabetes
New strategies are currently investigated, aiming to generate insulin-producing
cellsfor the replacement of deficient β cells. These strategies include differentiation
of stem cells or progenitor cells, as well the transdifferentiation of mature non-β islet
cell types. Characterization of the mechanisms of transdifferentiation, identification
of key factors involved in the process and their interactions are essential for success
in such strategies.
Proteomics has emerged as one of the most powerful tool available to scientists
forhigh-throughput screening, makes possible the detection and monitoring
ofprotein profiles in various conditions. Different technologies, including mass-
spectrometry and protein arrays represent the main approaches that allow
thecharacterization and validation of the process of cell transdifferentiation. Protein
arrays have the advantage of being very specific and having the ability to detect
endogenous proteins, even in the presence of related heterogenous species. One
of multiplex solutions, Luminex xMAP, is available and recommended for the assays
of secretory molecules in transdifferentiated cells. Thus, a Bio-Plex Pro Human
Diabetes 10-Plex Assay kit was selected and used to revealthe modified protein
signatures due to transdifferentiation.
Acknowledgement: COP- E 2016 Contract no. 148/2016, ID: P_37_794, My SMIS
No.: 106897, PN 19.29.01.04

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CIRCULATING LYMPHOCYTES
AND DENDRITIC CELLS POPULATIONS
AND SUBPOPULATIONS IN PSORIASIS
Mihaela Surcel1,2, Adriana Narcisa Munteanu1,2, Carolina Constantin1,3,

Gheorghița Isvoranu1, Ioana Ruxandra Pîrvu1, Adina Claudia Ionescu1,2,
Gabriela Coman4, Vlad Voiculescu5, Teodora Supeanu6, Mihail Alecu4,
Cornel Ursaciuc1, Monica Neagu1,2,3
1
“Victor Babes” National Institute of Pathology, Bucharest;
2
Faculty of Biology, University of Bucharest; 3Colentina University Hospital,
Bucharest; 4“Dr. Victor Babeş” Hospital, Bucharest;
5
University of Medicine and Pharmacy “Carol Davila”, Bucharest;
6
Research Laboratory, Romvac Company S.A, Romania
Introduction. Psoriasis (Ps) is a T-cell mediated chronic inflammatory disease

with a significant impact on the quality of life and a strong psycho-social pattern. Ps
pathophysiology is characterized by keratinocytes hyper-proliferation and immune
cell infiltration in the dermis and epidermis. Innate and adaptive immune cells are
highly involved, and among other cells, important cellular players being dendritic cells
(DC) and T lymphocytes (Ly).
Materials and methods: Ly and DC populations along with their subpopulations
were quantified using flow-cytometry peripheral blood from Ps patients as follow:
total T cells (CD3+), B cells (CD3-CD19+), NK cells (CD3-CD16+CD56+), T helper cells
(CD3+CD4+), T supressor/cytotoxic cells (CD3+CD8+), regulatory T (Tregs) cells
(CD4+CD25+CD127-), myeloid (M)DC (CD11c+CD304-) and plasmacytoid (P)DC
(CD304+CD11c-). The values were reported to a group of normal subjects.
Results: The main registered changes were the significant decrease of
T-CD8+percentages (p=0.0003) for all tested patients and elevated T-CD4+/T-CD8+
ratio (p=0.002) and T-CD4+ percentages (p=0.0002) in75% of cases. T-regs values
were elevated in 75% of patients, and the mean values of Tregs were significantly
(p=0.05) increased in Ps group (7.2±1) as compared to controls (5.6±1). Analysis of
DCsubpopulations revealed significant decreased values for both mDC (p=0.008) and
pDC (p=0.04).
Conclusions: The observed changes in lymphocytes subpopulations suggest
an imbalance of the immune response in sense of hyper-activation. Ps patients are
characterized by a quantitative deficit of circulating DC, and the decrease in the
percentage of MDC and PDC may be due to their recruitment at the lesion level.
Acknowledgement: PN19.29.01.01; PN19.29.02.03; PN-III-P1-1.2-PCCDI-2017-0341;
Grant COP A 1.2.3., ID: P_40_197/2016, Ctr. 52/2016.

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INFLAMMATION AND WNT SIGNALING

IN OSTEOARTHRITIS
Nagy Előd1,2, Horváth Emőke3,4

1
Department of Biochemistry and Environmental Chemistry, University of
Medicine, Pharmacy, Science and Technology Târgu Mureș;
2
Laboratory of Medical Analysis, Clinical County Hospital, Târgu-Mureș;
3
Department of Pathology, University of Medicine, Pharmacy, Science and
Technology Târgu Mureș; 4Laboratory of Pathology, Clinical Emergency
Hospital Târgu-Mureș, Romania.
Osteoarthritis is a multifactorial disease, involving abnormal mechanical

load, enhanced oxidative stress and chronic, low-grade inflammation. During
the course of the disease, almost all cell types of the joint: synovial fibroblasts,
macrophages, chondrocytes and subchondral osteoblasts show characteristic
phenotype changes. Subchondral osteoblasts and osteoclasts, synovial M1-type
macrophages and senescent chondrocytes release inflammatory mediators which
can diffuse through the subchondral bone-cartilage interface. Both sclerotic
and non-sclerotic osteoblasts are important sources of Cox-2 that triggers IL-
1β, IL-6, and up-regulate catabolic effector enzymes, like MMP-3,9,13. Altered
OPG-RANKL-RANK signaling combined with abnormal mechanical load leads
to a pro-inflammatory phenotype in one subtype of osteoarthritic osteoblasts
which become high PGE2, IL-6 and OPG producers. Several molecules of the Wnt
signaling system are implicated in subchondral bone sclerosis and concomitant
cartilage degradation. Wnt signaling exerts an opposite dual effect on subchondral
bone and cartilage. Activation of these metabolic pathways contributes to the
destruction of the articular cartilage by enhancing degradative processes and
contributing to the loss-of- phenotype in chondrocytes, with aberrant collagen-
and deficient aggrecan synthesis. Some Wnt inhibitors, e.g. sclerositin suspend
these phenomena. In contrast, intact Wnt signal-transduction concurrently
leads to subchondral bone remodelling, a transformation also characteristic for
osteoarthritis. Hence, alterations and imbalance in the activation or repression
of Wnt-mediated osteo-articular homeostasis are important risk factors for the
appearance and evolution of osteoarthritis.

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BIOLOGICAL AIMS OF VACCINATION
Corina Cianga1,2, Petru Cianga1,2

1
Department of Immunology, “Grigore T. Popa” University of Medicine
and Pharmacy of Iasi, Romania;
2
Laboratory of Immunology, “St. Spiridon” Hospital, Iasi, Romania.
When Edward Jenner made public his results regarding the protection against
smallpox after immunization with the live cowpox virus at the end of the 18th
century, he could not offer as well a physiopathological explanation for this
phenomenon. There were no information at that time neither about the cross-
reactivity between the two viruses, nor about the way the immune system works.
Even though the efficiency of a prophylactic vaccine is commonly evaluated
in terms of increase of serum concentration of the specific anti-pathogen
antibodies, an increase that is generically called “seroconversion”, it is important
to stress that the real aim of this active immunization procedure is to induce an
as long as possible B and T cell memory.
The production of antibodies is particularly useful when fighting extracellular
pathogens, hence seroconversion will not necessarily offer accurate information
regarding the protection against an intracellular pathogen, best dealt by the
means of a cellular immune response. Furthermore, the life span of the antibody
molecules is rather limited, in accord to their isotypes.
Both the anamnestic humoral immune responses of the B cells and the
anamnestic cellular immune responses of the T cytotoxic cells depend upon the
appropriate stimulation offered by the T helper cells. In conclusion, the main
objective to be fulfilled by an efficient vaccine is to induce a vigorous T dependent
immune response, able to induce the differentiation of the effector lymphocytes
into memory cells.

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COMPLEXITY OF VACCINE DEVELOPMENT

THROUGH TRANSLATIONAL RESEARCH: FROM
CONCEPT TO PRECLINICAL EVALUATION
Adrian Onu1,2, Norica Nechita3, Crina Stăvaru1, Gheorghe Savuta4,
Yuksel Rasit5, Mihaela Gherghiceanu6
1
“Cantacuzino” National Military-Medical Institute for Research-
Development Bucharest, Romania; 2Faculty of Pharmacy, “Titu Maiorescu”
University Bucharest, Romania; 3Institute of Biochemistry, Bucharest,
Romania; 4Faculty of Veterinary Medicine “Ion Ionescu de la Brad”
University of Agricultural Sciences and Veterinary Medicine, Romania;
5
Institute for Chemical - Pharmaceutical Research and Development –
ICCF Bucharest, Romania; 6“Victor Babes” National Institute of Pathology,
Bucharest, Romania.
As a major strategic direction in public health, vaccination benefits far outweigh

other means of protection against many infectious diseases, by eliminating, eradicating
or reducing morbidity and complications associated with infectious diseases. However,
we are living times when, even though the benefits of vaccination are obvious, excessive
and unfiltered information leads to decreased confidence in the vaccine. Therefore,
scientific arguments need to be continually provided to demonstrate the efficacy,
safety of vaccines and improve concepts related to their use.
Continuous development of new antigens is required, methods of characterization
are to be constantly improved and the reduced antigenicity of purified microbial
components requires the presence of adequate adjuvants. Therefore, the framework
required for vaccine development is achieved through studies that involve a better
characterization of the antigen, optimization of its formulation, extension of the
ways of characterizing the immunogenicity, evaluation of the protection and, finally,
the elaboration of the documentation of the non-clinical studies according to the
pharmaceutical regulations, with the main purpose of growth and strengthening
of scientific performance in the field of vaccinology. The studies performed on
models on the laboratory animal require accredited methods and facilities that
ensure appropriate technical-scientific skills in the field of vaccinology, in a strict
regimental framework.
The current presentation reviews all the above-mentioned elements.
Work supported by the Ministry of Research and Innovation, CCCDI - UEFISCDI,
project number PN-III-P1-1.2-PCCDI-2017-0529 / 62PCCDI ⁄ 2018, from PNCDI III.

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DIFFERENTIATION AND MATURATION

OF MURINE BONE MARROW DERIVED
DENDRITIC CELLS FROM FRESH AS OPPOSED
TO CRYOPRESERVED CELLS
Irina Elena Ionescu1, Iuliana Caraș1, Calin Tucureanu1,

Raluca Elena Lăzărescu, Ana Șerbănescu, Crina Stăvaru1, Adrian Onu1,2
1
“Cantacuzino” National Military-Medical Institute
for Research-Development Bucharest, Romania;
2
Faculty of Pharmacy, “Titu Maiorescu” University Bucharest, Romania.
Dendritic cells (DC) are essential in the induction of the adaptive immune
responses because they can activate naive T-cells and they can steer these adaptive
responses by integrating and coordinating various stimuli such as cytokines and
pathogen associated molecules. Because there is a strong need for a high efficiency
monitoring and characterization of vaccine development, dendritic cell-based in
vitro assays can be designed to evaluate the immunogenicity of candidate vaccines
and adjuvants during the process of research and development.
In our studies, bone marrow dendritic cells (BMDCs) derived from cells cultured
in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) to
induce differentiation into naive BMDCs and treated with LPS (lipopolysaccharide)
for maturation were used as a promising tool for capturing and presenting antigens
for in vitro vaccine characterization. To establish a highly efficient andreproductible
protocol and to reduce the number of animals used for experiments, fresh and
cryopreserved bone marrow cells were cultured under the same condition and their
expression of classical dendritic cell surface markers (CD11c, MHCII, and CD86) were
analysed by flow cytometry. Results obtained from these studies have important
implications for the upcoming interpretation of a broad array of data obtained
with DC culture systems and aim to contribute to the development of standardised
protocols for the quality control of the immune response to vaccination.
The work is supported by the Ministry of Research and Innovation, PCCDI -
UEFISCDI, project number PN-III-P1-1.2-PCCDI-2017-0529 / 62PCCDI ⁄ 2018, from
PNCDI III (CONVAC).

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MASS SPECTOMETRY CHARACHERIZATION

OF VACCIE ANTIGENS – APPLICATION
TO INFLUENZA FRAGMENTATION
Cătălin Țucureanu1, Vlad Vasilca1, Vlad Tofan1, Alina Lenge1,

Mihaela Lazar1, Adriana Costache1, Crina Stăvaru1 and Adrian Onu1,2
1
for Research-Development Bucharest, Romania;
2
Faculty of Pharmacy, “Titu Maiorescu” University Bucharest, Romania.
While not as efficient as live attenuated viral preparations, split inactivated

vaccines dominate the market due to a better safety profile in sensitive populations
(children, elderly, etc.) and fewer/lower magnitude vaccine associated side-effects.
Fragmentation conditions are highly dependent on the viral strain involved, minor
variations in the aminoacid sequence or glycosylation patterns having a strong
impact on splitting efficiency, aggregation and stability of the vaccine preparation.
In this study we have adapted protein painting, a technique initially developed
for the analysis of protein/protein interactions, to probe solvent exposure of viral
proteins in whole or split viral preparations in order to allow semiquantitative
comparison of fragmentation conditions.
Whole inactivated or split inactivated NIBRG-14 influenza virus reassortant was
incubated with or without remazol brilliant blue - RBB, denatured in SDS, reduced
and subjected to tryptic proteolysis. Peptides were separated by Nano-LC, analyzed
on a MALDI-TOF/TOF mass spectrometer.
A large number of peptides derived from abundant virion proteins (HA, M1, NP)
were identified while low copy number proteins (M2, NA) where less represented, but
detectable irrespective of sample treatment conditions. Taken separately, peptides
with modified abundance in RBB treated samples were relatively constant in split/
unsplit virus preparations for proteins normally exposed on the viral surface, while
being significantly less abundant for internal virion proteins in split preparations.
Thus, solvent accessibility of internal viral proteins can be used to assess the degree
of fragmentation in split-inactivated viral vaccines.
Work supported by the Ministry of Research and Innovation, CCCDI-UEFISCDI,
project number PN-III-P1-1.2-PCCDI-2017-0529/62PCCDI ⁄ 2018, from PNCDI III.

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OPTIMIZATION OF BACTERIAL EXPRESSION

OF ANTIGENS FOR VACCINE DEVELOPMENT
– APPLICATION IN INFLUENZA VACCINE
Laura Andreea Ermeneanu1, Vlad Tofan1, Cătălin Țucureanu1,

Vlad Vasilca1, Alina Lenghel1, Adriana Costache1,
1
“Cantacuzino” National Medico-Military Institute for Research and
Development, Bucharest, Romania;
2
“Titu Maiorescu” University, Faculty of Pharmacy, Bucharest, Romania.
Although no longer a new approach in vaccine manufacturing, bacterial

expression of proteinaceous antigens, despite its numerous advantages such as
low cost, high turnover and simplicity, is still encountering difficulties. Due to lack of
posttranslational modifications capabilities of bacterial host, different codon usage,
overwhelming synthesis rate, excessive optimization is often required in order to
generate lucrative amounts of pure high-quality protein that can be successfully be
used in immunizations and vaccine preparations.
Building upon Influenza A virus (strain A/Puerto Rico/8/1934 H1N1) hemaggluti-
nin (PR8) as a model protein we sought to improve antigen solubility and to ensure
correct folding of protein expressed in bacterial systems. As PR8 hemagglutinin
could only be obtained in insoluble form, we engineered two truncated forms that
preserve the main epitopes, retain trimerization ability and attain proper folding:
the HA1 segment and the slightly larger ectodomain segment.
We tested protein expression in E.coli strains and further optimized medium
composition and growth parameters in order to improve yield and partition into
soluble form.
As both proteins contain a His-TAG, purification was performed using affinity
chromatography followed by various polishing purification steps to generate highly
pure protein.
This study demonstrated the benefits of optimizing of protein sequence to
achieve bacterial expressed antigens for use in vaccine development.
Work supported by the Ministry of Research and Innovation, CCCDI – UEFISCDI,
project number PN-III-P1-1.2-PCCDI-2017-0529/62PCCDI/2018, from PNCDI III.

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EVALUATION OF DIAGNOSTIC MARKERS FOR

MEASLES VIRUS INFECTION IN THE CONTEXT
OF AN OUTBREAK IN ROMANIA
Cătălina Pascu, Carmen Maria Cherciu, Maria Elena Mihai, Mihaela Lazăr

and Development, Bucharest, Romania
A measles outbreak occurred from January 2016 to July 2019 in Romania,

despite the fact that the Plan of Eradication of Measles and its surveillance program
had been set up years ago. Different diagnostic markers for measles virus infection
were compared for 7,000 patients in tests of serum, urine, and pharyngeal exudate
specimens. Measles virus immunoglobulin M (IgM) levels in serum were assayed.
qRT-PCR was done on pharyngeal exudates, urine, serum and necrotic samples, and
isolation of measles virus in the VeroSLAM cell line was attempted. A total of 5,968
cases were diagnosed by qRT-PCR and IgM detection methods. The results for 5,663
(94,8%) were positive only by IgM detection. Besides, 2 PCR-positive IgM-negative
cases suggested either secondary vaccine failure or reinfection. Numbers resulting
from qRT-PCR performed with pharyngeal exudates and necrotic samples proved
to be significantly higher than those obtained with other specimens. Phylogenetic
analysis showed the presence of genotype B3 and D8. The results strongly back
the World Health Organization recommendation that detection of IgM should be
supplemented by qRT-PCR and isolation for the diagnosis of measles virus infection
for all sporadic cases and outbreaks in regions reaching or achieving measles
elimination.
Acknowledgments: We thank Emilia Dobre, Luiza Ustea, Nicoleta Paraschiv,
Mirela Eneand Oana Vitencu for technical assistance. We are very grateful to all our
colleagues from the Romanian local public health departments for sending specimens
of suspected measles cases and national measles surveillance coordinators: Aurora
Stănescu and Adriana Pistol from National Centre for Communicable Diseases
Surveillance and Control, National Institute of Public Health, Bucharest, Romania.

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MAIN OBJECTIVES IN THE PRODUCTION OF

VACCINES/ADJUVANTS AND THEIR ACCES/
MAINTENANCE TO MARKET. REGULATIONS
Iuksel Rașit1, Mariana Văduva2
1
National Institute for Chemical - Pharmaceutical Research
and Development – ICCF Bucharest;
2
for Research-Development Bucharest, Romania.
The strict production and development requirements that a vaccine must

comply with in order to obtain marketing authorization are regulated by WHO (and
Scientific Committees), EMA, Ministry of Health and National Regulatory Authority.
Like “conventional” medicines, vaccine development is a complex and long-
term process, but unlike the first ones, which address the treatment of a disease,
the vaccines are intended for the healthy population as a preventive measure. The
development and production of vaccine/adjuvant comprises the following stages
and objectives:
Non-clinical (preclinical) studies - necessary to determine the safety profile of
the vaccine, adapting the manufacturing technologies and selecting the antigen/
adjuvant, by performing both in vitro and in vivo tests. All information is essential
for the initiation of further clinical studies.
Phase I clinical trials - human testing on volunteers to evaluate safety, dosage
range and vaccine-related side effects.
Phase II clinical trials - in the case of convenient results obtained in Phase I,
potential vaccine is administered to a consistent group of healthy volunteers to
complete safety data, immunogenicity assessment, accurate dose setting and
schedule.
Phase III clinical trials - performed on thousands of subjects, assessing safety
and efficacy upon the target population of the vaccine and co-administration of
other vaccines.
Phase IV - Pharmacovigilance studies, after marketing, for strict surveillance of
vaccine safety by acquiring data on possible adverse reactions after immunization,
but also to obtain evidence that the protection offered by the vaccine is long-
lasting.
The work is supported by the Ministry of Research and Innovation, CCCDI -
UEFISCDI, project number PN-III-P1-1.2-PCCDI-2017-0529 / 62PCCDI ⁄ 2018, from
PNCDI III

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ANTI-TUMORAL EFFECTS OF SOME

NATURAL COMPOUNDS ON HEAD
AND NECK CANCER CELLS
Marinela Bostan1,2, Georgiana Gabriela Petrică-Matei3,

Gabriela Ion1, Mirela Mihăilă1, Camelia Hotnog1, Viviana Roman1,
Lorelei Irina Braşoveanu1
1
“Stefan S. Nicolau” Institute of Virology, Center of Immunology, Bucharest,
Romania; 2“Victor Babeș” National Institute of Pathology, Bucharest,
Romania; 3Department of Cytogenetics, Personal Genetics - Medical
Genetics Center, Bucharest, Romania.
Head and neck squamous-cell carcinoma is a complex disease characterized by

clinical, pathological, phenotypical, and biologic heterogeneity. The present study
aims to investigate whether the combined treatment of some natural compounds
(e.g. Ganoderma lucidum, Resveratrol/ Rsv) and cisplatin/ Cis (a platinum-based
chemotherapy drug) might give stronger anti-proliferative and/or apoptotic effects
in head and neck tumor cells as compared to single treatments. The influences of
natural compounds and/or cisplatin treatments were investigated in human oral
squamous cell carcinoma BICR-18 by means of Non-Radioactive Cell Proliferation
assay, flow cytometry methods (distribution of the cell cycle phases and apoptotic
events), and ELISA assays (evaluation of antigen expression of p21, Bax). Results
showed that treatment of BICR-18 cells with G. lucidum or Rsv had a cell proliferation
inhibition effect compared to treatment with cisplatin alone. Cell cycle analyses
performed on Ganoderma, BICR-18 treated cells as compared to nontreated cells
showed that the growth inhibition effect was associated with G2/M arrest and up-
regulation of p21 antigen expression, while Rsv treatment caused G0-G1 cell arrest,
without affecting p21 expression. Ganoderma lucidum or Rsv treatment significantly
induces apoptosis in tumor cells BICR-18, a process that may be associated with
increased expression of pro-apoptotic protein Bax. Furthermore, the treatment of
BICR-18 cells with G. lucidum or Rsv significantly enhances apoptosis induced by
cisplatin. In conclusion, our findings suggest that natural compounds used could
exert anti-tumor effects on BICR-18 tumor cells and enhance their sensitivity to
cisplatin.

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HISTOLOGICAL CHANGES IN MANGANESE

CHLORIDE INDUCED TOXICITY IN BALB/C MICE
Claudiu Gal1,2, Mariana Văduva1, Mihaela Diaconu1,3, Crina Stăvaru1

1
and Development, Bucharest;
2
USAMVB, Faculty of Veterinary Medicine of Bucharest;
3
University of Bucharest, Faculty of Biology, Bucharest, Romania.
The present study aimed to evaluate histological lesions induced by the

MnCl2dihidrate acute and subacute toxicity by intraperitoneal, subcutaneous and
oral administration. Groups of five BALB/c female mice received three times per
week a dose of 150 mg/kg (body weight) of MnCl2 in sterile solution, injected
intraperitoneally for 14 days, subcutaneously for 20 days, and a dose of 500 mg/kg
by oral gavage for 28 days. A control group received oral gavage with sterile 0.9%
saline solution.
Freshly collected tissue samples of liver, lung, heart, pancreas, spleen, kidney,
adrenal gland, ovary, uterus, bone, skeletal muscle, stomach, intestine, encephal
and cerebellum were formalin fixed, paraffin embedded, 5 μm thick sectioned and
hematoxylin-eosin stained.
In the intraperitoneal administration all mice presented hepatic lesions, with
moderate, acute hepatitis, mainly perilobular, mild steatosis, and mild, acute
cholangitis. Two mice presented a mild, acute, neutrophilic peritonitis and steatitis,
one also with mild pancreatitis. The subcutaneous administration group had
mainly ulcerative dermatitis, panniculitis and myositisat the injection site, mild
subacute hepatitis, and only one of them mild cholangitis, with edema. Mice with
oral gavage manifested moderate, acute, hyperplastic gastritis, two of them with
erosions and mild hemorrhages in the fundic regions, and three mice with mild
lymphoplasmacytic hepatitis. In the control group one mouse presented a mild
lymphoplasmacytic hepatitis and two mice, mild gastritis.
MnCl2 solution administered intraperitoneally and subcutaneously can induce
mild to moderate hepatitis but also has a local irritative effect, seen also in the
stomach mucosa of the oral gavage group.
This work is supported by the Ministry of Research and Innovation, project
number PN-III-P1-1.2-PCCDI-2017-0737.

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NATURAL KILLER CELLS FROM DIABETES

- PHENOTYPIC CHARACTERISTICS
Gheorghiţa Isvoranu1, Emilia Manole1, Mihaela Surcel1,2,

Adriana Narcisa Munteanu1, Ioana-Ruxandra Pîrvu1,
Monica Teodora Neagu1,2
1
“Victor Babeș” National Institute of Pathology, Bucharest, Romania;
2
Introduction: Treatments for type 1 diabetes are aimed at resetting the adaptive
arm of immune system, the innate immune system being often ignored in the design
of novel immune-based therapies. In this study, we show in a streptozotocin induced
diabetes mouse model that NK cells from the spleen are reduced as percentage and
have other phenotypic characteristics than NK cells from the healthy mouse.
Methods: We used C57BL/6 male mice, 8-10 weeks old. We analysed the
phenotypic characteristics of NK cells in a single dose streptozotocin induced
diabetes. After 5 days from intraperitoneal administration of streptozotocin the
spleens were harvested and immediately used for assessing the flow cytometry
analyses. Stained cells were analyzed with a FACSCanto II flow cytometer using
DIVA software. Normal values were established in healthy, age-matched mice.
Results: Experimental data show a statistically significant reduction of the
percentage of NK cells in diabetic mice in comparison with healthy animals. Splenic
NK cells expressed higher levels of CD69, CD28, CD11c, gp49R, CD45R, CD25and
lower levels of CD49b, CD43, NKp46, CD11b, CD132, CD122.Analysis of NK cell
subsets, defined by the differential expression of a combination of CD27 and
CD11b, indicated a significant difference in the distribution of NK cell subsets with
the mature subset being dominant in the healthy mice.
Conclusions: Our study has provided new insights into NK cell phenotype in
diabetesas future new approaches to diabetes immunotherapy.
Acknowledgement: This work was partially supported by Core Program,
implemented with the support NASR, projects nos. 19.29.02.03 and 7PFE/16.10.2018.

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EVALUATION OF ANTI-TUMOR ACTIVITY

FOR AN ALCOHOLIC EXTRACT OF TAMARIX
GALLICA FROM ROMANIA
Ioana Mădălina Pitica1, Lilia Matei1, Laura Denisa Dragu1,

Cristian Coman2, Mihaela Economescu-Chivu1, Irina Alexiu1,
Laura Georgiana Necula1, Cristina Mambet1, Ana Neagu1,
Saviana Nedeianu1, Carmen C. Diaconu1, Iuliana Crisan3, Coralia Bleotu1
1
“Stefan S Nicolau” Institute of Virology, Romanian Academy, Bucharest,
Romania; 2“Cantacuzino” Institute, Bucharest, Romania;
3
S.C. HOFIGAL Export Import S.A., Bucharest, Romania.
Tamarix gallica is a source of phenolic compounds which present biological

properties: anti-inflammatory, antioxidant, hepatoprotective, chemoprevention,
antimicrobial, etc. activities, these properties being determined by the origin region.
In our study we evaluated the biologic effects of the T. gallica extract from Romania
on different cell lines, at cellular and molecular level. The obtained results could
elucidate the T. gallica mechanism of action in different pathologies.
Materials and methods: Treated and untreated cells were evaluated in flow
cytometry regarding the cell cycle distribution and cell viability. In order to
characterize the apoptotic events a carboxifluorescein multi-caspase activity kit,
Annexin V-FITC/PI detection by flow cytometry, protein quantification for active
caspase-3, Bcl-xL/Bak dimer, Mcl-1/Bak dimer, Survivine using xMAP technology
and, also, a Proteome Profiler Array - Human Apoptosis Array Kit were performed.
Results: The treatment with T. gallica extract induced G2/M arrest of eukaryotic
cells, the percentage of cells arrested in this phase increased when treated with a
higher concentration. The multi-caspase activity kit showed an increased caspase
activity in treated cells vs. untreated ones. Moreover, the pro-apoptotic proteins
levels were increased and anti-apoptotic, Bcl xL and IAP family members (Survivin,
cIAP 1 and cIAP 2), were decreased. Also, T.gallica extract increased the levels of
caspase 3 and the cytochrome c.
Conclusion: In our study, the T. gallica extract proved pro-apoptotic activity and
also induced G2/M arrest, sustaining its anti-tumor potential.
Acknowledgements: This work was supported by CNCSIS–UEFISCSU project
PCCDI III-116 BG/2016 and structural funds POS CCE O2.2.1. 433/2012.

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THE IMMUNOMODULATORY ACTIVITY

OF CHELIDONIUM MAJUS L. EXTRACT
Ioana Mădălina Pitica1, Lilia Matei1, Laura Denisa Dragu1, Cristin
Coman2, Mihaela Economescu-Chivu1, Irina Alexiu1, Laura Georgiana
Necula1, Cristina Mambet1, Ana Neagu1, Saviana Nedeianu1, Carmen C.
Diaconu1, Iuliana Crisan3, Coralia Bleotu1
1
“Stefan S Nicolau” Institute of Virology, Romanian Academy, Bucharest,
Romania; 2“Cantacuzino” Institute, Bucharest, Romania;
3
S.C. HOFIGAL Export Import S.A., Bucharest, Romania.
Chelidonium majus L. belongs to Papaveraceae family and is spread through the

entire world, including Europe, Asia, Northwest Africa and North America. This plant
contains different alkaloids, organic acids, carotenoids, and flavonoids, and is well
known for its antiviral, anti-inflammatory, anti-tumour, etc. activities. The aim of our
study was to evaluate the immunomodulatory activity of the extract of Chelidonium
majus L. from Romania.
Materials and Methods: The immunomodulatory activity of alcoholic C. majus
L. extract was evaluated in vitro, on HT-29 cells by evaluating IL1b and IL6 genes
expression using qPCR, as well as by analysing the influence on immunomodulatory
factors at protein level on THP1 cells using xMAP technology. The immunomodulatory
activity in vivo was evaluated on CD1 mice (after administration of tested extract)
by evaluating IL1b and IL6 genes expression in colon using qPCR, along with
investigating the plasma levels of some cytokines/chemokines using ELISA
technique.
Results: C. majus L. extract induced pro-inflammatory IL-1b and IL-6 gene
expression in vitro and similar effects were observed in vivo. At protein level, the
tested extract increased IL-17a, IP-10 and TNFa levels, and decreased IL-2 level in
cell culture supernatant. In vivo, the increased levels of IL-12 and IL-10, as well as of
IL-2 and IL-4, point to a protective effect induced by this extract.
Conclusion: Chelidonium majus L. proved an immunomodulatory effect on the
immune system both, in vitro and in vivo. Still, further studies are needed in order
to establish C. majus L. anti-inflammatory activity mechanism of action.
Acknowledgements: This work was supported by CNCSIS–UEFISCSU project
PCCDI III-116 BG/2016 and structural funds POS CCE O2.2.1. 433/2012.

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COLLAGEN-INORGANIC NANOPARTICLES
COMPOSITES FOR WOUND HEALING
Denisa L. Dragu1, Lilia Matei1, Sabina Zurac3, Ionela Andreea Neacsu2,
Anton Ficai2, Ana I. Neagu1, Mihaela Chivu-Economescu1, Bianca Tihuan4,
Ecaterina Andronescu2, Carmen Cristina Diaconu1, Coralia Bleotu1
1
“Stefan S Nicolau” Institute of Virology, Romanian Academy, Bucharest;
2
Faculty of Applied Chemistry and Materials Science, University Politehnica
of Bucharest; 3UMF “Carol Davila”, Bucharest, Romania;
4
SANIMED, Calarasi, Romania.
Considering the growing incidence of chronic wounds, the development of

advanced wound dressings, such as combinations of nanoparticles with biopolymers,
are necessary to improve the wound healing process. In this context, our goal was
to investigate, in vivo, the efficacy of nanocomposite collagen sponges embedded
with ZnO and SiO2@ZnO inorganic nanoparticles.
Materials and Methods: The wounds were created onto the dorsum skin of
eight to ten-week-old white CD1 mice, using an 8-mm diameter biopsy punch.
Each injured areas was covered with a collagen sponge embedded with different
concentration of ZnO and SiO2@ZnO nanoparticles. The healing process was
monitored in time by digital photography, and tissue regeneration and inflammatory
responses were evaluated by immunohistochemical analysis and RT-PCR.
Results: Photographic evaluation of the wounded areas indicated an accelerate
healing process in the presence of a higher concentration of ZnO nanoparticles.
Immunohistochemical evaluation reveals the presence of alpha-smooth muscle
actin expression in granulation tissue myofibroblasts four days post-implantation,
which indicates the initiation of the healing process. Also, in the case of complexes
with higher concentrations of ZnO nanoparticles, the cytokine profile evaluation
indicated an increased expression of IL-1, TNF-α, and IL-6, as well as increase the
production of Caspase-1.
Conclusion: Nanocomposite collagen sponges embedded with ZnO and SiO2@
ZnO inorganic nanoparticles speed up the initiation of the healing process, but
more data are required to establish efficacity of the collagen sponges embedded
with ZnO and SiO2@ZnO inorganic nanoparticles.
Acknowledgments: This work was supported by CNCSIS-UEFISCSU project PN-
III-P2-2.1-52PTE/2016 and structural funds POS CCE O2.2.1. 433/2012.

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BIOLOGICAL EFFECTS INDUCED BY DRUG

TREATMENTS ON PROLIFERATION OF MCF-7
BREAST CANCER CELLS
Mirela A. Mihăilă, Camelia Mia Hotnog, Marinela Bostan, Viviana

Roman, Ion Gabriela, Lorelei Irina Brașoveanu
“Stefan S. Nicolau” Institute of Virology, Center of Immunology, Bucharest
Breast cancers are malignancies with high incidence, being the second cause
of mortality throughout women. Breast tumor cell invasion and metastasis involve
aberrant progression of the cell cycle, evasion of apoptosis, modification of cell
adhesion, being the result of multiple genetic and epigenetic damages to the cell,
involving proto-oncogenes and tumor suppressor genes, resulting in the generation
of a malignant phenotype, and resistance to chemo-/radio-therapy.
Our studies, based on different lab techniques, showed the modulation roles
of bioactive compounds (Resveratrol/RSV), added to oncolitical treatments
(Adriamicin/ADR), at gene and protein levels of molecules associated to apoptosis,
proliferation, with consequences on the biological behaviour of MCF-7 cells.
The MCF-7 human breast adenocarcinoma cell line was treated with different
concentrations of ADR/RSV for 24h, and percentages of cell lysis, apoptotic events,
gene vs. protein expression of selected apoptosis-related molecules (p53, Bax, Bcl-
2) were investigated. Compound-mediated cytotoxicity was evaluated by MTS and
Real-Time Cell Analysis (RTCA) assays. Flow cytometry techniques were used to
analyze modulation of apoptosis, while levels of protein expression were evaluated
both by indirect immunofluorescence, followed by flow-cytometry, and Western
blotting. Gene expression was investigated after cells were processed to obtain
cDNA, and probes were used to perform RT-PCR analysis in the TaqMan system. Our
results indicated a higher sensibility of breast cancer cells to lysis when combined
treatments are used, increased levels of apoptosis, and higher gene and protein
expression of pro-apoptotic molecules (p53/Bax). New therapeutic strategies for
breast cancer are needed to improve clinical outcomes for breast cancer patients.

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MODULATION OF ANGIOGENIC MARKERS

IN COLON CANCER CELLS WITH DIFFERENTIAL
TP53 MUTATIONAL STATUS
Camelia Mia Hotnog, Mirela Mihăilă, Marinela Bostan, Lorelei Irina

Brașoveanu
“Stefan S. Nicolau” Institute of Virology, Center of Immunology, Bucharest
Tumor angiogenesis is a result of pro- and anti-angiogenic factors balance,

tumor invasion and metastasis being promoted by the up-regulation of angiogenic
factors, such as VEGF or endoglin (CD105). In the recent years, significant progress
has been made in finding anti-angiogenic strategies for tumor therapy. Since
many natural compounds, like curcumin (Crm), display anti-carcinogenic and
anti-proliferative effects towards colon cancer cells, recent studies focused on
the discovery of new biological agents that might be used as additives in colon
cancer prevention and treatments. In the present study, we have investigated the
modulation effects of anti-colon cancer drugs (5-fluorouracyl, 5-FU) and/ or CRM
on angiogenic protein profile in LoVo (wild-type p53) and HT-29 (mutated p53)
colon cancer cell lines. In addition, levels of VEGF and endoglin gene expression
were detected by RT-PCR. Briefly, cells were treated with 25uM 5-FU or 50 uM Crm;
after 24h cells were processed to obtain cell lysates and total protein amount was
quantified. The relative protein expression was determined by protein microarray
technique, using RayBio® Human Angiogenesis Antibody Array kit. Alternatively,
treated and non-treated cells were processed for mRNA extraction, purification,
reverse-transcription, and amplification with Taqman assays. Angiogenesis may be
regulated by the function of TP53 gene: the wild-type form of TP53 gene induces
the down-regulation of angiogenic factor expression, whereas a dysfunctional
mutated p53 stimulates angiogenesis by up-regulating VEGF. The obtained results
showed a differential expression of angiogenic markers in treated vs. untreated
colon cell lines under study, depending also of their p53 mutational status.

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ASTRO-IMMUNOLOGY: GENE EXPRESSION

PROFILE IN MONOCYTIC CELLS EXPOSED
TO SPACE-RELEVANT RADIATION
Gina Manda1, Ionela Neagoe1, Maria Dobre1, Elena Milanesi1,

Ulrich Weber2, Nicole Averbeck2
1
“Victor Babes” National Institute of Pathology, Bucharest, Romania;
2
GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany.
Introduction: Experimental evidence highlights that low-dose ionizing radiation

can disturb cell homeostasis at multiple levels due to the inflicted chronic low-
grade oxidative, inflammatory and genotoxic stresses that are known to underline
many chronic pathologies. Therefore, it is of utmost importance to investigate the
biologic impact of radiation exposure from a “network medicine” perspective.
Aim: To identify particular molecular networks activated in monocytes exposed
in vitro to space-relevant radiation and to develop a “proof of concept” study on
the therapeutic potential of NRF2 activators for counteracting radiation effects.
Results: The human monocytic cell line CRL-9855 (ATCC) was exposed at
GSI (Germany) to 56Fe beams (0.1-2Gy). Cells were investigated regarding their
response to radiation-induced stress by addressing a network of 84 genes (Qiagen,
Stress and Toxicity Pathway Finder). Preliminary results revealed important gene
expression changes at 48 hrs post-irradiation: 1) profound down-regulation of the
pro-apoptotic gene BBC3 which was only partially due to the down-regulation of
the tumor suppressor gene TP53; 2) moderate up-regulation of genes involved in
cell cycle arrest (CDKN1A and GADD45A), complemented by a significant down-
regulation of HUS1; 3) moderate upregulation of only some target genes of the
NRF2 transcription factor, such as the HMOX1, AKR1B1, GSTP1 and TXNRD1 genes,
while other target genes were down-regulated (GCLC, GCLM and GSR).
Conclusion: Pharmacologic stimulation of the NRF2 pathway as a master
regulator of more than 250 cytoprotective genes is a promising therapeutic
strategy to reinforce the cytoprotective equipment of normal cells in the stressful
spaceflight environment.
Acknowledgement: Work was supported by the grant PCCDI_35/2018 and by
the grant AO-2017-IBER_003/2018 (European Space Agency).

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CANCER STEM CELL MARKERS CORRELATED

WITH ANGIOGENIC FACTOR AND CYTOKINE
LEVEL IN GLIOMA
Maria Linda Popa1,2, Adrian ClaudiuPopa3, Ana-Maria Enciu1,2,
Ionela DanielaPopescu1, Elena Codrici1, Simona Mihai1, Laura Necula1,4,
Lucian Albulescu1, CristianaTanase1,5
1“Victor Babes” National Institute of Pathology, Proteomics Department,
Bucharest, Romania; 2“CarolDavila” University of Medicine and Pharmacy,
Cellular, Molecular Biology and Histology Department, Bucharest,
Romania; 3Army Center for Medical Research, Bucharest, Romania;
4
“Stefan S. Nicolau” Institute of Virology, Bucharest, Romania;
5
“Titu Maiorescu” University, Cajal Institute, Bucharest, Romania.
The increasing frequency of brain tumors in the recent years, together with
their severity and lack of efficient management, especially of glioblastoma, has
determined an increased interest in fundamental research in this field. An important
role in tumorigenesis, the particular aggressiveness and tendency to recurrence of
these tumors has been attributed to the presence of cancer stem cells.
The present study focuses on revealing markers useful in identifying the
presence of cancer stem cells in glioma, such asCD133, Nestin, C-kit, Notch1-4. In
glioblastoma derived cell cultures, most cells have shown a moderate expression
of stem cell markers, whereas 5-10 % were intensly positive, which could identify
them as the reservoir of cancer stem cells responsible for the poor response of
high-grade glioma to classical therapeutical strategies.
From multiplex assay, a strong overexpression was detected for IL-6, IL-1β, TNFα
and IL-10. Significant up-regulation was found for VEGF, FGF-2, IL-8, IL-2 and GM-
CSF.
When stem cell markers are correlated with expression of cytokines and
angiogenic factors, a strong association is found in tumors with high aggressiveness
and invasiveness.
As these cancer stem cells may be responsible for intracranial tumor initiation and
aggressiveness, we are presently conducting concomitant inhibition of angiogenic
pathways and specific stem cell signaling (Notch signaling).
This work is supported by Grants PN-III.P1-1.1-PD-2016-2093, contract no.
121/2018and PN 19.29.01.04.

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MODULATION OF THE INFLAMMATORY

RESPONSE BY THE INTEGRATION OF BIOACTIVE
MATERIALS AT THE DENTAL PULP LEVEL
Khaled Al Ghieb1, Mihaela Itul Toderesc1, Bianca Gălăţeanu2,
Octav Ginghină3, Carolina Negrei1
1
Disciplina Toxicologie, Facultatea de Farmacie,
UMF “Carol Davila”, Bucureşti, România;
2
Facultatea de Biologie, Universitatea Bucureşti, Bucureşti, România;
3
Disciplina Chirurgie şi Anestezie Generală, Facultatea de Medicină
Dentară, UMF “Carol Davila”, Bucureşti, România
The initial inflammatory response that occurs in the carious (bacterial and acidic)
causes of hard dental structures and pulp tissue has the effect of regenerating the
dental pulp and creating hard protective tissues (reactiondentin). The destructive
role of continuous inflammation on the pulp tissue (via the B and T lymphocytes
of the acquired immune system that infiltrates the tooth pulp and contributes to
the inflammatory response in the tissue and once activated by lipopolysaccharides,
mediates the destruction of the pulp tissues, secreting a series of cytokines (pro-
inflammatory and tissue degrading enzymes), a process that can lead to pulp
necrosis and periodontal damage to the tooth.
Modulation solutions of the inflammation in favor of tooth pulp preservation
and its vital maintenance can be done with scaffolds impregnated with substances
that reduce the bacterial cytotoxic effect on dental tissues. This way the tooth
capacity of self-regenerating (both of the mineralized tissues destroyed by the
bacterial infection, but also of the pulp tissues) can be effectively exploited. It will
be emphasized the need to decrease the inflammation induced by bacteria on the
pulp, to suppor tand facilitate its regeneration.
According to the literature, stem cell transplantation can be extremely useful
in the processes of regeneration, revitalization and revascularization of the pulp
tissues, especially in cases where the dental pulp is completely missing at the level
of that tooth.

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ASSESSMENT OF PROLIFERATION,
CYTOTOXICITY AND APOPTOTIC EFFECTS
INDUCED BY NANOPARTICLES
Elena Codrici1, Alexandra Cătălina Vîlceanu2, Ionela Daniela Popescu1,
Simona Mihai1, Ana-Maria Enciu1,2, Lucian Albulescu1, Radu Albulescu1,3,
Codorean Eleonora1, Mircea Leabu1, Butu Alina4,
Cristina Mihaela Luntraru5 and Cristiana Tănase1,3
1
“Victor Babes National Institute of Pathology, Bucharest, Romania;
2
3
“Titu Maiorescu” University, Faculty of Medicine, Bucharest, Romania;
4
Institute of Biological Sciences, Bucharest, Romania;
5
Hofigal Export-Import SA, Bucharest, Romania.
Introduction: Green synthesis of nanoparticles (NP) represents anenvironmentally-

friendly and efficient method based onvarious plant extracts in order to generate metal NP.
Methods: Several cell types: monocytes (CRL9855), primary epidermal keratinocytes
(HEKs), dysplastic oral keratinocyte (DOKs) and aggressive tumor cells-glioblastoma cell
line (U87) were used to evaluate the effects of NP obtained by green synthesis (Ag, Au, Pd,
Se metals and plant extracts from Levisticumofficinale, Origanumvulgare). The methods
used were MTS assays for viability measurements, LDH assay for cytotoxicity, xCELLigence
- electrical impedance measurements and Luminex xMAP array for apoptosis evaluation
in cell lysates.
Results: The results of MTS and LDH assays, on monocytes cell lines, showed that metal
salts alone express higher cytotoxicity than green NP, due to the fact that toxicity was
reduced by plant extracts; the vegetal extracts alone had proliferative effects. xCELLigence
measurements showed a dose-dependent proliferative effect for some of the studied
NP. Luminex xMAP array revealed typicaleffects for apoptosis in tumoral cells: activation
of caspase-9 during treatment with Ag-based NP, correlated with the results for p53,
suggesting that Au and Ag-based NP induced p53-mediated apoptosis in tumor cells by
DNA fragmentation, correlating with decreased Bcl-2 expression.
Conclusions: Our results confirmed that these NP could induce apoptosis in tumoral
cells through caspase activation. Green synthesis represents a sustainable technology,
being a nontoxic and safe option for biomedical applications, thus improving NP in terms
of biodegradability, functionalization, and biocompatibility.
Acknowledgement: Partially supported by the grant COP A 1.2.3., ID: P_40_197/2016,
Ctr. 52/2016 and by Ministry of Research and Innovation in Romania, under Program 1
– The Improvement of the National System of Research and Development, Subprogram
1.2 – Institutional Excellence – Projects of Excellence Funding in RDI, Contract No.
7PFE/16.10.2018, and PN19.29.01.04
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DYSPLASTIC EPIDERMAL CELLS ARE ONLY

PARTIALLY AND TEMPORARYPROTECTED
FROM UV-A IRRADIATION BY SEA
BUCKTHORN OIL TREATMENT
Dudău Maria1, Alexandra Cătălina Vîlceanu2, Ana-Maria Enciu1,2,

Elena Codrici1, Simona Mihai1, Ionela Daniela Popescu1,
Lucian Albulescu1, Isabela Tarcomnicu3, Cristiana Pistol Tănase1,4
1
2
3
SC Cromatec Plus SRL Bucharest, Romania;
4
“TituMaiorescu” University, Bucharest, Romania.
Introduction: Sea buckthorn (Elaeagnusrhamnoides (L.) is a unique medicinal and

aromatic plant, rich in fatty acids and flavones. Sea buckthorn alcoholic extracts or seed oil
were tested repeatedly for antioxidant, antitumor and regenerative properties.
Aim: Our study aimed to test whether cold pressed sea buckthorn oil had a protective
effect against UVA irradiation on human skin cells.
Material and method: Two epidermal cell lines (normal adult keratinocytes –NHEK
(Lonza) and dysplazic keratinocytes - DOK (ECACC) were irradiated with UVA for 30 mins and
tested for changes in cell adherence and proliferation in presence or absence of non-toxic
doses of cold pressed sea buckthorn oil. Treatment dose of oil was selected by MTS and LDH
assays. Oil uptake was assessed by OilRed staining. Cell adherence and proliferation were
tested by real-time impedance reading and video microscopy.
Results: UVA irradiation of both normal and dysplastic epidermal cells impaired both
cell adhesion (during the first two hours of substrate attachment) and proliferation, but only
transiently. During the 24 hours post UVA exposure, irradiated cells regained proliferative
activity to match the non-irradiated ones. Post irradiation treatment with cold pressed sea
buckthorn oil aggravated the adhesion and proliferation impairment, but showed no effect
on non-irradiated cells. 72 hours pretreatment of cells partially rescued the effect of UVA
irradiation, but on long term it favored the proliferation of dysplazic cells.
Conclusion: Cold pressed sea buckthorn oil could have a protective effect against
detrimental UVA irradiation, but only as a preventive treatment. On long term, the oil
treatment can enhance proliferative abilities of dysplastic cells, while having no effect
on normal cells. The benefits and disadvantages of skin applications should be carefully
weighted.
Acknowledgments: This work was funded by grant COP A 1.2.3., ID: P_40_197/2016.

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MUSCLE DAMAGE AND NON-INVASIVE

STRATEGY FOR TISSUE REGENERATION
Gisela Găină1,2, Emilia Manole1,3

1
2
Department of Biochemistry and Molecular Biology, University of
Bucharest, Romania;
3
Colentina Clinical Hospital, Bucharest, Romania.
Muscle injury can be induced by a variety of factors such as mechanical damage,

muscle pathology, infections pathogens and biochemical toxicities. The changes
occurred at muscle level produce initially an inflammatory response that involves
activation of inflammatory cells followed by activation and differentiation of
satellite cells, leading to full structural and functional healing of muscle injuries.
Because more physiological mechanism issue in the skeletal muscle remains an
unsolved, there is a great interest in a better understanding of both molecular
mechanisms of skeletal muscle damage and repair as well as in the involved factors
in the inflammation process (anti-inflammatory cytokines IL-4, IL-10, IL-13) which is
considered as key element in the pathological progression of the disease. Several
studies have shown that low laser level therapy (LLLT) accelerates tissue repair
and skeletal muscle regeneration. These findings suggested the possibility using
of this method as therapeutic approaches for treating muscle injuries. There are
few evidences that suggest a potential therapeutic effect of low laser level (LLL)
in modulating the expression of anti-inflammatory cytokines, pro-inflammatory
cytokines (IL-1β, IL-2, IL-6), tumor necrosis factor-α (TNFα) and NF-κB transcription
factor. Further research will be necessary to explore laser irradiation parameters
(wavelength, power, frequency, dosage, exposure time) and evaluation of their
potential effect on the cellular and molecular expression of the reactive oxygen
species (ROS), muscle repair factors (MyoD, Myf5, MRF4), as well as human telomeric
repeat binding factors TRF1 and TRF2, that control the telomere lengths and play a
pivotal role in tissue repair.

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A NOVEL WORK FLOW FOR THE EXTRACTION

OF MELANOMA ANTIGENS FROM FORMALIN
FIXED PARAFFIN EMBEDDED SPECIMENS
Teodora Grigore1, Adina Dobre1, Anca Filimon1,
Sabina Zurac2, Gabriela Negroiu1
1
Department of Molecular Cell Biology, Institute of Biochemistry of
Romanian Academy;
2
Department of Anatomopathology, Colentina Clinical Hospital, Bucharest,
Romania.
Cutaneous melanoma (CM) is an extremely heterogenous tumor with an insidiuos

progression. The identification of novel regulators of melanoma pathways, potentially
diagnostic/prognostic or therapeutic targets are under continous investigation.
Dopachrometautomerase (DCT) is a melanoma antigen with multiple functions
including tumor resistance to environmental and therapeutic stress.
DCT assessment in histological evaluation of CM revealed specimens with DCT-
high levels, dissociated from tyrosinase (Tyr) (the gold molecular standard in melanoma
identification). The molecular architecture of these specimens have always DCT in the
lower part of tumor components (middle, deep dermis) whereas Tyr remains in the upper
part or is totally absent. Moreover, the DCT-high specimens are associated with bad/
unfavorable prognostic clinical parameters.
To identify the proteins emblematic for DCT-high specimens Formalin Fixed Paraffin
Embedded (FFPE) melanoma specimens were used.
We present here the workflow of an optimized procedure, selected from eight
variants, for retrieving proteins from FFPE specimens representing Superficial Sspreading
Melanomas (SSMs) or Nodular Melanomas (NMs). The selected samples were previously
stained for DCT/Tyr by immunohistofluorescence. Specimens were dewaxed and
rehydrated followed by tissue extracted in Tris-buffer containing DTT and glycin, two-steps
of incubation under controlled temperature and sonication. The soluble material retrieved
after centrifugation was analyzed by western blotting for DCT expression comparatively
with positive controls, represented by melanoma cell lysates. In both SSMs and NMs
DCT was identified by western blotting at correct molecular weight as in controls, which
practically validated this method.
The material retrieved by applying this workflow is suitable for further proteomic
analysis by mass spectrometry.
Acknowledgements: This work was supported by Grant Application no 61-PCCDI-2018,
National Programe PN-III-P1-1.2 PCCDI-2017, funded by Ministry of Education and
Scientific Research.
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THE IMPORTANCE OF THE IMMUNOLOGICAL

DIAGNOSIS FOR PATIENTS WITH
TOXOCARIASIS AND ALLERGIC SYMPTOMS
Patricia Mihăilescu1,2, Carmen-Michaela Crețu1,3, Claudia Istrate1
1
Eco-Para-Diagnostic SRL, Bucharest, Romania;
University of Bucharest, Faculty of Biology, Bucharest, Romania;
2
3
University of Medicine and Pharmacy Parasitolgy Department,
Bucharest, Romania.
Introduction: Toxocariasis is a disease caused by the infection with Toxocaracanis/

cati, parasitic nematodes-order Ascaridia. The nematode lives as adult, in the small
intestine of his definitive host (dog/cat). Human being is an accidental host, where
the life cycle of the parasite is interrupted in the larval stage. After ingestion of the
infective eggs, larvae migrate via vascular system spreading through the organs,
Liver, lungs, central nervous system, eyes are mainly affected. General symptoms
are: fever, liver, spleen enlargement, lower respiratory signs, eosinophilia (70%),
hypergammaglobulinemia, increased levels of IgE and allergic symptoms.
Materials and methods: The study was performed in Eco-Para-Diagnosis
Medical Center, Bucharest: 01.01.2017–30.05.2019. 2799 blood samples were tested
for Toxocara specific antibodies. Methods: screening-ELISA (1258), avidity (943);
confirmatory - Western Blot (598).
Results: Blood samples were collected from patients belonging to both sexes
and all age groups. ELISA samples: 343/1258 positives (27.26%), 915/1258 negatives
(72.74%).67/943 (7.10%) samples tested for avidity showed a recent infection and
203/598 (33.94%) confirmed an infection using WB. From the WB positives samples
38/203(18.71%) were ELISA positives.90 (44.33%) from the confirmed patients
showed allergic symptoms and a high level of IgE.
Conclusion: Laboratory diagnosis of toxocariasis using immunological methods
are excellent tools which provide a lot of information about clinical involvement.
Our results demonstrate that the most affected age groups are children (<10y.o.)
and adults over 50y.o. all these being correlate with allergic symptoms. This will be
an advantage for the patients with a weak immunological status, who will receive
the specific treatment for them.

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INFLAMMATION-RELATED PATTERNS
IN CHRONIC KIDNEY DISEASE ASSESSMENT
Simona Mihai1, Elena Codrici1, Ionela D. Popescu1, Ana-Maria Enciu1,2,

Lucian Albulescu1, Cristina Mihaela Luntraru3, Gabriela Anton4
and Cristiana Tănase1,5
1
“Victor Babeș” National Institute of Pathology, Biochemistry-Proteomics
Department, Bucharest; 2“Carol Davila” University of Medicine and
Pharmacy, Cellular and Molecular Medicine Department, Bucharest;
3
Hofigal Export-Import SA, Bucharest; 4“Stefan S. Nicolau” Institute of
Virology, Molecular Virology Department, Bucharest; 5“Titu Maiorescu”
University, Cajal Institute, Faculty of Medicine, Bucharest, Romania.
Chronic kidney disease (CKD) is a condition characterized by an irreversible loss of

kidney function, representing a global health burden. Mineral bone disorders (MBDs)
constitute a hallmark of CKD and, alongside cardiovascular complications, underlie
the poor prognosis for patients. In this scenario, our study focused on novel CKD
biomarker patterns and their impact on staging and severity of the disease. The relative
expression levels of 105 proteins were assessed by Proteome Profiler Cytokine Array
Kit for pooled CKD stages 2–4 serum samples. Among the molecules that displayed
significant dysregulation in CKD stages, we have further explored the involvement
of Dikkopf-related protein 1 (Dkk-1), a recognized inhibitor of the Wntsignalling
pathway, and its crosstalk with calcitriol as new players in renal bone and vascular
disease. Their serum level was quantified by ELISA (on 76 samples) and the results
revealed decreasing circulating levels of Dkk-1 and calcitriol in advanced CKD stages,
with their circulating expression showing a downward trend as CKD develops. In the
next step we analyzed the inflammation and MBD biomarkers’ expression in CKD (by
Luminex xMAP array). Our results showed that the moleculesinvolved in orchestrating
the inflammatory response, IL-6 and TNFα, as well as the mineral biomarkers
osteoprotegerin, osteocalcin, osteopontin and fibroblast growth factor 23, were
correlated with Dkk-1 and calcitriol, raising the possibility of them being potential
useful biomarkers. Our results revealed the impact of different biomarker patterns in
CKD stagingand severity, thus opening up novel approaches to be explored in CKD
clinical management.
This work was supported by Ministry of Research and Innovation in Romania, under
Program 1 – The Improvement of the National System of Research and Development,
Subprogram 1.2 –Institutional Excellence – Projects of Excellence Funding in RDI,
Contract No. 440 7PFE/16.10.2018, grant COP A 1.2.3, ID: P_40_197/2016, and PN
19.29.01.04.
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BIOCOMPATIBILITY PROPERTIES
AND REGENERATION ACTIVITIES
OF COLLAGEN-BASED BIOMATERIALS
Ionela Daniela Popescu1, Elena Codrici1, Simona Mihai1,

Ana-Maria Enciu1,2, Lucian Albulescu1, Radu Albulescu1,
Mihaela - Adi Lupu3 and Cristiana Tanase1,4
1
2
3
SC Sanimed International Impex SRL;
4
“Titu Maiorescu” University, Faculty of Medicine, Bucharest, Romania.
Background: Collagen is the most abundant protein in the human body. Over the
recent years, collagen-based biomaterials have been intensively applied in the field of
regenerative medicine. Collagen has various advantages in terms of biodegradability
and biocompatibility, being highly versatile and easily available.
Methods: We have investigated the collagen obtained from natural sources
compared to commercial collagen, using in vitro methods to evaluate cytotoxicity and
regenerative activity. Cytotoxicity and proliferation testing was performed using the
LDH and MTS assays, on ATCC-CRL-9855 cell lines, in standard conditions, at different
cell concentrations (10.000 – 50.000 cells/well), at different times of exposure (24h,
48h) and different collagen concentrations (15-150 μg/mL). xCELLigence cell index
(CI) impedance measurements were performed according to the manufacturer’s
instructions.
Results: The investigated collagen types did not show significant cytotoxic effects
(LDH and MTS assays) over the concentrations ranging 15-150 μg/ml. Our results
illustrated comparative effects of novel tested collagen in comparison to the commercial
type. The xCELLigence assay also shown a cellular proliferation/regeneration induced
by collagen compounds, in a dose - dependent manner.
Conclusions. The combination of in vitro assays could represent an effective
screening tool for the discovery of innovative collagen-based biomaterials with large
applications in the regenerative medicine field.
Acknowledgment: Partially supported by the grant COP A 1.2.3., ID: P_40_197/2016,
Ctr. 52/2016 and by Ministry of Research and Innovation in Romania, under Program 1
– The Improvement of the National System of Research and Development, Subprogram
1.2 – Institutional Excellence – Projects of Excellence Funding in RDI, Contract No.
7PFE/16.10.2018, and PN 19.29.01.04.

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ABSTRACTE
JOI, 19 SEPTEMBRIE 2019

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THE RELEVANCE OF HIGH RESOLUTION HLA

TYPING FOR THE BEST MATCHED DONOR IN
HEMATOPOIETIC STEM CELL TRANSPLANTATION
Larisa Denisa Vişan1,2, Ana Moise1,2, Adela Maria Toader¹,

Corina Andreea Rotărescu1,2, Mirela Maria Iacob¹, Ion Mărunţelu1,2,
Andreea Mirela Caragea1,2, Adriana Tălăngescu¹, Ileana Constantinescu1,2
1
Centre for Immunogenetics and Virology, Fundeni Clinical Institute,
Bucharest, Romania;
2
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania.
Introductionː Hematopoietic Stem Cell Transplantation (HSCT) is a curative

treatment in leukemia, lymphoma and non-malignant diseases. There is a growing
demand for matching donors with patients for long-term survival.
Aimsː Our aim was to determine the immune genetics factors that have an impact
on successful HSCT. We have focused on HLA (human leukocyte alleles) donor/
recipient matching and herpes virusses status in order to assess their impact on
post-transplant events such as graft-versus-host disease (GvHD), rejection, relapse or
transplant-related mortality.
Patients and Methodsː The study has been performed on 182 patients who
underwent an HSCT transplant, with at least one year of follow-up. Both, related and
unrelated donor-recipient pairs were considered. In the majority of cases (84.6%) the
HLA compatibility between recipient and donor was 100%, and only 28ofpairs (15.4%)
had one allele mismatch occurred in the HLA-A locus (4 cases with related HSCT, and
24 with unrelated HSCT).
HLA high-resolution genotyping was performed with sequence specific primers
(SSP) and sequencing based typing (SBT) methods (One Lambda kits).
Resultsː The allogeneic transplant offer late donor-recipient pairs, shows lower
rates of acute/chronic GvHD, rejection, rate of relapse and transplant-related mortality
(tRM) compared with unrelated pairs.
Conclusionsː HLA matching is crucial in HSCT and current high-resolution HLA
typing methods has improved results of allogeneic transplants. The better level of HLA
matching has assisted in reducing the incidence of post-transplant events.

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DYNAMICS OF CHIMERISM MONITORING,

MANAGEMENT OF IMMUNOSUPPRESSIVE
THERAPY AND VIRAL INFECTIONS IN
ALLOGENEIC HEMATOPOIETIC STEM CELL
TRANSPLANTED PATIENTS
Corina Andreea Rotărescu1,2, Ana Moise1,2, Larisa Denisa Vişan1,2,

Ion Mărunţelu1,2, Andreea Mirela Caragea1,2, Mirela Maria Iacob1,
Adriana Tălăngescu1, Ileana Constantinescu1,2
1
Centre for Immunogenetics, Fundeni C.I., Bucharest, Romania;
2
Immunology and Transplant Immunology, “Carol Davila” UMF,
Bucharest, Romania.
Introduction: Among standard therapeutic strategies in patients with blood

cancer, allogeneic hematopoietic stem cell transplantation remains the only potentially
curative treatment option. Chimerism monitoring is useful to evaluate the integration
of donor hematopoietic stem cells. Immunosuppressive therapy helps to prevent
allograft rejection, but is commonly associated with the occurrence of post transplant
viral infections.
Materials and methods: This study analyzes 76 patients who underwent related
and unrelated allogeneic stem cell transplantation in Bone Marrow Transplant Center,
in Fundeni Clinical Institute. Chimerism monitoring was performed by STR (short
tandem repeats) methodology (Mentype Chimera), the blood level of the immune
suppressants was evaluated by chemiluminescence (Architect, Abbott), and for
viremias assessment we have used real-time polymerase chain reaction (Anatolia
Geneworks).
Results: After the first month post transplant, chimerism value of 100% donor
cells was present in 71%of patients, commonly in patients who received intensive
immunosuppressive therapy. They also had an increased risk to develop viral infections
(42,5% cases of cytomegalovirus reactivation, 24,3% cases of BK virus activation, 2,6%
cases with reactivation of Epstein-Barr virus, 1,3% cases of reactivation Parvovirus B19).
Conclusions: Chimerism monitoring in bone marrow transplanted patients is
significantly useful due to early predictive value for relapse onset. Chimerism results
could also be related with the risk of viral infections reactivation. Early specific
detection and treatment of viral infections is an important issue in hematopoietic
stem cell transplantation follow-up.

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APPROACHING NGS IN HLA TYPING

– THE CLINICAL REVELANCE IN HSCT FOR
UNRELATED COMPATIBLE DONOR SEARCH
Ileana Constantinescu1,2, Ana Moise1,2, Larisa Denisa Vişan1,2, Ion

Mărunţelu1,2, Adriana Tălăngescu1, Mirela Maria Iacob1, Corina Andreea
Rotărescu1,2, Andreea Mirela Caragea1,2, Marina Manea1,3
1
Bucharest; 2“Carol Davila” University of Medicine and Pharmacy,
Bucharest; 3Laboratory of Medical Analyses I, Fundeni Clinical Institute,
Bucharest, Romania.
Introduction: With rapid development and wide applications of next-generation

sequencing (NGS) technologies genomic sequence information is an important and
accurate tool for HLA genes matching with a large impact on life expectancy in
Hematopoietic Stem Cells Transplantation (HCST).
Material and Methods: NGS systems possess a tremendous sequencing
capacity which enables us to produce in a short time big HLA (human leucocytes
alleles) data for best donor – recipient HLA matching.
Results: Our work reveals the NGS technology advantages in comparation with
Sanger SBT (Sequencing Based Typing) and high resolution SSP (Sequence Specific
Priming) method for typing the HLA genes.
Conclusion: In HLA typing the challenge is to solve alleles ambiguities and
produce accurate results for both donors and recipients. It seems that NGS
exhibit better performance in terms of read length, accuracy, applications and
bioinformatics infrastructure.

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ASPECTS OF PEDIATRIC IMMUNOLOGY IN

APPROACHING KIDNEY TRANSPLANTATION
IN CHILDREN
Andreea Mirela Caragea¹˒², Adriana Tălăngescu¹, Ana Moise¹˒²,

Larisa Denisa Vişan¹˒², Mirela Maria Iacob¹, Ion Mărunţelu¹˒²,
Corina Andreea Rotărescu¹˒², Ileana Constantinescu¹˒²
1
Bucharest, Romania;
2
Introduction: Transplantation is the optimal therapeutic approach, significantly

improving the quality of life for pediatric patients suffering from chronic end-stage
renal disease.
Aims: Understanding the aspects of transplantation immunology is essential in
the correct management of pediatric renal graft recipients to correctly diagnose
acute or chronic rejection
Patients and Methods: Evaluation of human leucocyte antigen (HLA) typing
was performed using the Inno Train Sequence Specific Primers (SSP) method, with
Ready Gene Online software being used for interpretation. Determination of Class
I and Class II anti-HLA antibodies was performed using LAB Screen Single Antigen
reagents with Luminex® xMAP technology. To determine the crossmatch test, we
have used the Lifecodes DSA Donor Specific Antibody Detection kit, Immucor for
Class I and Class II.
Results: In Fundeni Clinical Institute, Centre for Uronephrology and Renal
Transplantation between 2013 and 2018, were transplanted a number of 26 pediatric
patients from the Fundeni Clinical Institute. We used various variables for each
patientː blood type, the cause of chronic renal disease, gender, age of the patient,
blood transfusion, dialysis, HLA typing for class I and class II for the recipient,
donor type (related, unrelated) donor, crossmatch assay, anti-HLA antibody and
immunosuppressive regimens.
Conclusions: Understanding the clinical features of transplant immunology in
children who have received or are about to receive a renal graft is essential for the
proper management of this group of patients.

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ASPECTS OF ALLELIC HLA POLYMORPHISMS IN

PATIENTS WITH CHRONIC KIDNEY DISEASES
UNDERGOING KIDNEY TRANSPLANTATION
Ion Mărunțelu1,2, Daniela Filofteia Nedelcu1, Ana Moise1,2,

Adela Maria Toader1, Larisa Denisa Vișan1,2, Corina Andreea Rotărescu1,2,
Mirela Maria Iacob1, Adriana Tălăngescu1, Ileana Constantinescu1,2
Centre for Immunogenetics, Fundeni C.I., Bucharest, Romania;

1
2
Introduction: Chronic kidney diseases (CKD) evolves, in most cases, to the

end stage of kidney failure (ESKF). Our purpose was to determine whether specific
class I and class II HLA genotypes could be associated with CKD progression to
ESKF, regardless of other factors.
Materials and methods: The HLA alleles were assessed in 444 patients with
CKD admitted in Fundeni Clinical Institute. As control group we have considered
450donors. HLA genotyping was performed at different degrees of resolution
levels using SSP methodologies.
Results: In the patients’ group, we have found that only HLA-C*15 allele
was associated with ESKF. When we have analyzed HLA genotypes for the same
locus, we have noticed that the genotypes B*35,*51, C*07,*15, C*02,*07and the
homozygous variant C*07, DRB*15 and DQB*02 were associated with chronic
kidney failure.
Conclusions: Our results revealed that HLA Class I/II alleles could be directly
associated with the progression of CKD to the ESKF. These findings highlight
interesting information which enable clinicians to decide for a better diagnostic
and prevention strategy for such kind of patients.

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CHARACTERIZATION OF DONOR-SPECIFIC
ALLOREACTIVE CD4+ AND CD8+ CELLULAR
IMMUNE T CELL RESPONSES IN THE LUNG
ALLOGRAFT AND BLOOD IN LUNG
TRANSPLANT RECIPIENTS
Iulia Popescu1, Carlo Iasella2, Elizabeth Lendermon1, Spencer Winters1,
John Sembrat1, Melissa Saul3, Xiaoping Chen1, Nouraie Seyed1, Brianna
Hewitt1, Ritchie Koshy1, Yingze Zhang1, Wei Xu1, Vera Iouchmanov1, Mark
Brown1, Bruce Johnson1, Silpa Kilaru1, Matthew Morrell1, Joseph Pilewski1
and John McDyer1
Division of Pulmonary, Allergy and Critical Care Medicine, Department
1
of Medicine, University of Pittsburgh, USA; 2School of Medicine School

of Pharmacy, University of Pittsburgh, USA; 3Institute of Discovery,
Department of Medicine, University of Pittsburgh School of Medicine; USA.
Purpose: Lung transplantation remains the only therapeutic option for select patients with end-
stage lung diseases, however chronic lung allograft dysfunction (CLAD) significantly limits long-term
survival in lung transplant recipients (LTRs). Episodes of acute cellular rejection (ACR) are common
and the major risk factor for developing CLAD, however little is known about donor-specific cellular
T cell responses, as these have not been previously characterized in LTRs.
Methods: We used a novel ex vivo flow cytometric assay to assess donor-specific alloimmune
responses from LTRs cells in lung allograft resident effector T cells (BAL-derived) and PBMC. Using
a 6h in vitro re-stimulation protocol with either irradiated donor cells or donor lysate, we measured
the frequencies of effector responses (IFN-γ, TNF-α, the cytotoxic marker CD107a, IL-17a, IL-13,
IL-2 and the co-stimulation surface molecule, CD154) from CD4+ and CD8+ lung resident or blood
compartment T cells.
Results: Overall the predominant alloreactive effector responses were donor-specific CD154
surface expression following in vitro re-stimulation with donor lysate in lung resident CD4+ T cells
compared to the PBMC compartment, with minimal to absent expression on CD8+ T cells. Expression
of surface CD154 was highly co-expressed with allo-specific CD4+ T cells producing the Type-1
cytokines IFN-γ, TNF-α and CD107a suggesting CD154 as a marker for Type-1 effector function, but
not Type-2 or Type-17 responses. In fact, donor-specific IL-13 and IL-17 responses were detectable
in some patients but at significantly lower frequencies compared to Type-1 effector responses,
suggesting a hierarchy of allo-effector immune responses. Comparison between the lung resident T
cells and blood T cells revealed consistently increased donor-specific alloreactive frequencies in the
lung allograft versus the periphery. Ongoing experiments are assessing the proliferative capacities
of donor-specific alloreactive T cell populations in the blood compartment.
Conclusion: Together, these data indicate donor-specific alloreactive effector CD4+CD154+ lung
resident T cells activated via the indirect allorecognition pathway are present in high frequencies in
LTRs with histologic evidence or history of ACR and segregate to Type-1 effector cytokine responses.
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PEDIATRIC PSORIASIS – WHAT’S NEW?
Daciana Elena Brănişteanu1, Cătălina Ioana Brănişteanu1, Andreea

Dimitriu2
1
Discipline of Dermatology, University of Medicine
and Pharmacy “Grigore T. Popa” – Iaşi;
2
Department of Dermatology, Arcadia
- Spitale si Centre Medicale, Iasi, Romania.
Pediatric psoriasis is a common dermatosis. One-third of patients develop

psoriasis in childhood, the incidence of pediatric psoriasis increases with age.
Psoriasis is a multifactorial disorder with an important genetic background. The
HLA-Cw6 allele is often associated with increased susceptibility to psoriasis. HLA-
Cw6 is responsible for a more severe forms of the disease, with early onset and
with guttate lesions. The family prevalence of pediatric psoriasis is higher than at
the adult psoriasis. Pediatric psoriasis is associated with metabolic comorbidities
(obesity, diabetes, high blood pressure) and non-metabolic (atopy, epilepsy, vitiligo,
alopecia areata, celiac disease). The pediatric form differs from the adult form, it
associates more pruritic, thinner, softer and less scaly lessions. Plaque psoriasis is
the most common form, followed by guttate, pustular and erythrodermic form. The
prevalence of psoriatic arthritis in children is 1-10%. Children have lesions especially
in the flexural, frontal, periauricular areas, and the diaper area is the specific
location of infants. Most of the pediatric population has a mild form of the disease,
which requires topical treatment according to age. For moderate-severe forms, not
responsive to topical therapy, UVB phototherapy with narrow band is preffered.
Systemic therapies are options for severe forms. The new therapeutic options are
biological therapy. Adalimumab, Ustekinumab and Etanercept are approved for
pediatric psoriasis, demonstrating efficacy and a good safety profile.
Pediatric psoriasis presents multiple challenges: specific clinical aspects, multiple
therapeutic options approved for adults are still studied in the pediatric population,
absence of clinical guidelines and therapeutic algorithms.

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HPV INFECTION. KEY MESSAGES
Daniel Boda
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
Human papilloma viruses (HPV) are a small group of non enveloped viruses
belonging to the Papillomaviridae family with strong similarities to polyoma
viruses. The viral particles consist of a genome in the form of a circular double
stranded DNA, encompassing eight open reading frames, as well as a non
enveloped icosahedral capsid. HPV infection is considered the most common
sexually transmitted disease in both sexes and is strongly implicated in the
pathogenesis of different types of cancer.
‘High risk’ mucosal HPV types, predominantly types 16, 18, 31, 33 and 35,
are associated with most cervical, penile, vulvar, vaginal, anal, oropharyngeal
cancers and pre cancers. Screening for HPV is necessary for the prognosis and
for determining treatment strategies for cancer. Novel HPV markers, including
proteomic and genomic markers, as well as anti papillomavirus vaccines are
currently available.
The aim of this oral presentation is to thoroughly present the updated
information on virus development, cancer occurrence, treatment and prevention
strategies, in an attempt to shed further light into the field, including novel
research avenues.

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TOO GOOD TO BE TRUE… AND YET…
Patricia Cristodor
Clinica Dermatologică, UMF “Victor Babeș” Timișoara, România
Though dermatologists usually do not pay a lot of attention to ectropion, it

is a quite frequent and annoying event. One may encounter it physiologically in
senescent, old people or as a result of surgery or trauma of the eyelids. For the
patients, it leads at least to a permanent discomfort if not to impared vision.
In 4 patients, 3 males and one female, aged from 58 to 90 years, we applied
an original method of treatment for the ectropion, consisting in repositioning
the palpebral skin by means of kinesiologic tapes. These tapes are non-allergenic
and elastic (their elasticity matches the elasticity of the skin).
We changed the tapes every 4-7 days. In all of our subjects we had positive
results: the ectropion was completely corrected in 2 patients and partially in the
other 2 during the next 2-3 weeks (the latter had severe ectropion and are still
under treatment).
We suppose that the tapes act by triggering a reorientation of the collagen
fibers in the dermis, but the precise mechanism is still unclear to us. We strongly
advise the surgeons to try this simple, painless, efficient and very cheap method
before enagaging in delicate, risky and painful surgical procedures.

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THE JOY OF EACH STEP!
Daciana Brănișteanu
UMF „Grigore T. Popa”, Iași; Sp. Sf. Spiridon Iași; DERMALUX, Iași
The feeling of heavy legs, on the border between symptom and perception,
affects the quality of life of many Romanians. Often ignored or overlooked, this
unpleasant situation concerns 30.5% of the population that addresses to the
family doctor *.
As a result of the questioning, almost 1 out of 3 people from the GP’s office
had this discomfort, without being able to formulate a diagnosis that would
incriminate any venous pathology. In the fight against this discomfort, of heavy,
tired legs, the affected people try multiple solutions. And over 50% of them are
trying a topic for hydration, energization, cooling *.
However, many of these solutions fail to respond to user needs. Servier
worked with the most best experts in luxury French cosmetics to develop the
new energizing foot cream, Cedraflon. This concept that combines science
(Servier’s expertise in the field of phlebology) with luxury (know-how behind the
big cosmetic brands), offers an answer for releasing the feeling of heavy legs,
bringing additional benefits: hydration, toning.
References:
VEIN DIRECTION - Adaptat din: Feodor T. International Angiology. 2016;
35:(Suppl.1):0316, p63
Nielsen – Consumer Insights, septembrie 2017

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PAIN – MANAGEMENT PRINCIPLES
Nicuța Manolache1, Gabriela Stoleriu1, Daciana Elena Brănișteanu2

1
“Dunarea de Jos” University of Galati, Faculty of Medicine and Pharmacy,
Research Center in the Field of Medical and Pharmaceutical Sciences,
Pharmacology Sciences Department, Galati, Romania;
2
“Grigore T. Popa” University of Medicine and Pharmacy,
Departament of Dermatology, Iași, Romania.
Are we alone against pain? Can we avoid pain? Can we fight pain? Is pain
part of our life? Does the human need pain? Theese are questions that are
preoccupying the medical world more and more, in the last decades a specific
attention being accorded to pain study.
The correct and complete pain management requires knowing the clinical
forms, the evaluation and therapy methods, the producing mechanisms, and
finding the remedies for fighting or lowering pain, requiring specialists from
almost every medical and pharmaceutical domain. In pain management, I
consider that the principle stated by the International Association for Pain Study
(AISP) is fundamental: «Every patient’s right to have his pain under controlis a
fundamental right of the human».
When facing each patient, let’s not forget that he/she has the right to dignity
and to a minimum life quality, correct pain treatment being a professional
obligation involving multiple ethics. The paper is supposed to be an invitation on
reflecting the importance of pain study.

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THE CHRONIC VENOUS DISEASE
Daniel Boda
“Carol Davila” University of Medicine and Pharmacy,

Bucharest, Romania
Nowadays, CVD is one of the most common disease having a high prevalence
(CVD is affecting 7 from 10 persons, according to Vein DIRECTION study, held
in Romania in 2015). Patients often ignore the manifestations of the CVD even
though CVD is a progressive, inflammatory disease with a significant impairment
of quality of life.
Patients addressability to doctor for CVD signs or symptoms for their own-
initiative is very low, only 1 from 4 patients are diagnosticated and optimal
treated for improving symptoms and clinical signs or for preventing the disease
progression.
The aim of the symposium is to present an overall view of the importance of
doctor’s involvement to participate actively in the diagnosis of CVD and into the
management of this disease.
First of all, an optimal management of CVD requires/involves a diagnosis
of venous circulation disfunction in the early stages by anamnesis, clinical and
paraclinical exams, Doppler Echo- with an important role in diagnosis. The rigorous
monitoring of the newly diagnosed patients or of the patients already under the
treatment is very important. The choice of the effective treatment according to
international guidelines in CVD is the key of an optimal management of CVD.

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CURRENT ADVANCES ON TELOMERES

RESEARCH
Tsatsakis A.1#, Tsoukalas D.2,3, Sarandi E.1,2, Thanasoula M.2,

Fragkiadaki P.1, Vakonaki E.1 and Renieri E.1
1
Laboratory of Toxicology, Medical School, University of Crete, Heraklion,
Greece; 2Metabolomic Medicine Clinic, Health Clinics for Autoimmune and
Chronic Diseases, Athens; 3Clinical Pharmacy and University of Medicine
and Pharmacy, Faculty of Pharmacy, Craiova, Romania;
Telomeres, the protective caps of chromosomes, shorten every time cells divide,
and the pace of telomere attrition is a robust marker of aging and aging-related
diseases. Shorter telomeres are associated with increased incidence of aging-
related diseases and shorter lifespan. The percentage of short telomeres and rate
of telomere shortening predicts longevity in mammals. We have developed a
semi-automated worksheet, BIOTEL, to generate individual and group leukocyte
telomere length statistics and provide a crude estimation of biological age. In a
group of 150 healthy individuals, age and sex was found to affect telomere length
and mostly length of short telomeres. Ongoing clinical studies from our group
will determine the factors that accelerate telomere attrition as novel anti-aging
targets. We have recently shown that supplementation with nutraceuticals was
positively associated with longer telomeres in a study of 47 healthy participants
suggesting a potential role in healthy aging. Thus,nutraceutical supplements may
be beneficial for themaintenance of telomere length through the decrease of
oxidation and chronic inflammation. In addition, activation of telomerase has
been shown to contribute to telomere length maintenance and stability. Thus,
modulators stabilizing telomeres and increasing telomerase expression / activity
has been proposed as potent in anti-aging. We have identified several natural
molecules that increase the telomerase activity. 08AGTL was the most potent
telomerase activator reported up to date, (up to 9-fold), and future in vivo studies
in rats and humans will unravel its mode of action and potency as anti-aging
modulator.

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AT THEFRONTIERS OF MEDICINE:
REGENERATIVE MEDICINE – TOO MANY
CHALLENGES, TOO LITTLE CERTITUDES
Florian Berghea1
1
Internal medicine and Rheumatology, UMF „Carol Davila”
București, Romania
Regenerative medicine is the field of many hopes linked to the potential

benefits of stem cell manipulation. From a rheumatologist point of view some
applications of regenerative medicine are of particular interest.
Cartilage regeneration, both in focal and in widespread lesions, are targeted
due to a large number of potential subjects that need this solution. Stem-cell
transplantation in systemic sclerosis is targeted due poor results of available
treatments used in this disease.
An update of available solutions and existing challenges in front of this two
situations will be presented.

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HISTORY OF THERAPEUTIC ANTIBODIES

AND NOBEL PRIZES
Georgeta Sinițchi
Allergy Medical Center “ATOPIA” – Iași, Romania
Polyclonal and monoclonal therapeutic antibodies (Ab) are to be considered

starting with the history of serotherapy. Emil von Behring received the Nobel
Prize in Medicine in 1901 for researching infectious diseases. Antidifteric vaccine
was the first vaccine manufactured. Nowadays, monoclonal antibodies are
biological target agents recognizing specific antigen, being the major therapeutic
innovation of the last 130 years. The production technique was published in 1975
by Georges J.F. Köhler and César Milstein for which they received the Nobel Prize
in 1984. We note that an important contribution was made by Rosalind Franklin,
the specialist in the analysis of diffraction photographs who helped showing
the double-propeller structure of DNA; “photo 51”is famous. Monoclonal Ab
are used as antiinflammatory, antitumoral, antiinfectious, anticolesterolemic
and antiallergic agents in severe asthma and severe dermatitis. Using
immunostimulants as anticancer drugs are constituted “a revolution in oncology”
and the discoverers, James P. Allison and Tasuku Honjo, received the Nobel Prize
in 2018. In conclusion, Monoclonal and Polyclonal Ab expanded new therapeutic
pathways, the discoverers are appreciated with the Nobel prizes.
Key words: history of serotherapy, polyclonal Ab, monoclonal Ab, oncological
immunotherapy, Nobel prizes.

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METABOLISM AND IMMUNE-METABOLISM

Prof. Dr. med. H. Joachim Seitz, Dir (em.)
Institute Biochem. Endocrinology, University Medical Center
Hamburg-Eppendorf
HIV-1 AND HLA-C: A MATTER OF STABILITY

Prof. Univ. Dr. Donato Zipeto
Department Neuroscience, Biomedicine and Movement Science,
School of Medicine, University of Verona, Italy

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ABSTRACTE
VINERI, 20 SEPTEMBRIE 2019
Conferință comună a Asociației Române

de Imuno-Dermatologie, a Societății de
Imunologie din România, a Societății Române
de Alergologie și Imunologie Clinică și a
Societății Române de Pediatrie

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THE IMPORTANCE OF IMMUNOPHENOTYPING

IN THE DIAGNOSIS AND THERAPY MONITORING
OF PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA
Anca Coliţă1
1
“Carol Davila” University, Fundeni Clinical Institute, Bucharest, Romania
Acute leukemia (AL) is the most common pediatric malignancy, representing 25-30% of all
malignant diseases. Acute lymphoblastic leukemia (ALL), accounting for 75% of pediatric AL,
is a heterogeneous disease, characterized by the proliferation and accumulation of immature
lymphoid cells initially in the bone marrow and, then in the peripheral blood, tissues and
organs. The long-term survival rate in pediatric ALL is 80-85%. The WHO classification of
lymphoid malignancy recommends renouncing the morphological classification of FAB
because it lacks clinical or prognosis value. The immunological classification includes 2 main
categories: B-cell and T-cell ALL. The AIEOP-BFM immunophenotypic classification of ALL
(table 1) using a wide panel of antibodies, allows the subtype classification and identification
of the leukemia associated immunophenotype, used in the monitoring of the minimal
residual disease (MRD).
Table 1. ALL
immunophenotypic
classification
MRD, defined as undetectable disease by morphological methods, is commonly

detected by multiparametric immunophenotyping. Monitoring of BMR at certain times
of treatment has contributed greatly to the classification in risk groups and adaptation of
therapy. Standardization of the immunophenotypic examination is essential for reducing
inter-laboratory variability (antibody panel, gating modalities, classification of intensity of
antigenic expression, subclones presence interpretation, etc.) and is a major element in
facilitating clinical application and therapeutic modulation.
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SKIN REGENERATION TECHNIQUES

Gabriela Stoleriu1,2, Cătălina Maria Voicu2, Daciana Elena Brănișteanu3,
Nicuța Manolache1, Florina Mihaela Filip-Ciubotaru4
1
“Dunărea de Jos” University of Galați, Faculty of Medicine and Pharmacy,
Department of Pharmaceutical Sciences; 2Derma Clinique, Iași; 3“Grigore
T. Popa” University of Medicine and Pharmacy, Iași, Faculty of Medicine,
Department of Dermatology; 4“Grigore T. Popa” University of Medicine and
Pharmacy, Iași, Faculty of Medicine, Department of Family Medicine
Skin aging is a complex biological process, influenced by endogenous and exogenous

factors. The main purpose of all anti-aging strategies is to stop the ageing process, but also
to induce the reversibility of dermal and epidermal degeneration, produced by chronological
aging and sun-exposure. The skin barrier has selective permeability if it is intact and
normally functioning, having an important mechanical and chemical protective role, acting
against: dehydration, allergens, irritants, free radicals and radiation, as well as against the
penetration of various microorganisms. Regenerative medicine is the science of replacing or
regenerating human cells, tissues or organs to restore or establish normal form and function.
Regenerative medicine uses cells, tissues, drugs, synthetic biomaterials and devices to help
the tissue healing or induce regeneration. By skin regeneration we are trying to increase
the elasticity, smoothing, density, improving the macroscopic and microscopic appearance,
improving the quality of the skin. At the same time, it is necessary to slow down the aging
process at the cellular level. We can supply the skin with primary structural constituents,
such as collagen, elastin, to prevent wrinkles, but some products and techniques promote
the natural synthesis of these constituents. At the same time, it is necessary to prevent the
formation of wrinkles by administration of topical or systemic antioxidants, in combination
with sunscreens and retinoids for enhanced effect. Important attention should be paid to
the family of growth factors, collagen, fibronectin, laminin, elastin, glycosaminoglycans and
other natural biomaterials. The regenerative aesthetic dermatology focuses on innovative
treatments that support the skin for rejuvenation and regeneration of the aged and / or
damaged skin, improving the quality, causing faster healing, reducing the recovery period
and the side effects. The onset of effects can be observed immediately after the procedure
or it can be installed gradually, with the increase of the effect over time (weeks or months),
because we determine the skin to help itself. The regenerative treatments favor the synthesis
of collagen and elastin itself through bio-stimulation: rejuvenation of the epidermis (topical
application of substances, ablative LASER, radiofrequency, JettPlasma, microdermabrasion
without crystals) neocolagen formation (IPL, LASER, radiofrequency, JettPlasma, infrared
irradiation, mesotherapy, platelet rich plasma, hyaluronic acid fillers, HydraFacial MD, gene
therapy), slow down the visible aging process, helping to reduce certain lines and dynamic
wrinkles (botulinum toxin). Skin rejuvenation can be considered a cancer prophylaxis, and
aesthetic dermatology contributes to a slow, healthy, graceful aging.
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PCR BASED MULTIPLEX DETECTION

OF MOST IMPORTANT DERMATOPHYTES
Markus Cavalar
EUROIMMUN Medizinische Labordiagnostika AG, Aachen
PCR based diagnostic test systems can identify pathogens in short term, while
traditional culture based methods may need several days. With new platforms
which are able to perform multi parameter testing, not only a detection but also
subtyping of the pathogen at the same time is possible.
Especially in the mycology, where the cultivation of fungus needs weeks,
culture pleomorphology makes visual species identification difficult and a
diagnostic very often fails completely, the use of modern PCR techniques are a
big advantage.
Detailed results make it possible to find the right antimycotic drug and
dosage which significantly increases the treatment success and decreases the
risk of relapses.

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CUTANEOUS MICROBIOM AND ATOPIC

DERMATITIS AT CHILD
Georgeta Sinițchi
Alergological Medical Center “Atopia” Iași, Romania
Atopic dermatitis is a frequent disease at child: over 25% and also at adult: over
10%. Multiple factors occur intrinsically and extrinsically: food and environmental
allergens, hereditary, genetic land, along with disruption of skin barriers.
An immune imbalance is believed to be the cause, namely the modification
of the LTh1 / LTh2 ratio in the favor of the last one and the increasing of the
interleukins: IL4, IL5, and TSLP. The cutaneous microbiom is a recently discussed
factor coupled with innate immunity. The cutaneous microbiom is the complex
of microorganisms present in the skin, comensus and symbiotic tissue. The
microbiozom, the virus, and the micome are discussed. Molecular biology based
on DNA amplification coding on bactrian ribosomes is noted today. Multiple
factors interfere with atopic dermatitis: cutaneous barrier, easier trans-epidermic
penetration of microorganisms, Staphylococcus aureus prevalence in atopic skin,
the importance of innate skin immunity and adaptive immunity that modulate skin
inflammation. In baby we notice the sensitization at the milk cow. The bacterial
biofilm, which is an agglomerate bacterian, is responsible for immune activation
with the production of inflammatory cytokines (TNFα and pruritic mediators).
Abnormalities of antimicrobial peptides would be another idea of participating
in the physical barrier. The therapeutics would be: systemic and topical antibiotic
therapy, fight against biofilms, restoration of TLR deficient activity (local agonists)
antiIL23 antibodies in intrinsic, topical forms with synthetic antimicrobial peptides:
ceragenine. Conclusions. The microbiom plays a role in atopic dermatitis.
Keywords: atopic dermatitisat child, microbial, Staphylococcus aureus,
‘Staphylococcus dermatitis’, molecular diagnosis.

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NEW PERSPECTIVES OF BIOLOGIC THERAPY

FOR CHILDHOOD ASTHMA
Carmen Panaitescu1,2
1
Department of Functional Sciences, UMFVBT, Timisoara, Romania;
2
OncoGen Research Center, SCJUT, Timisoara, Romania.
Asthma is a chronic inflammatory airways disease, with variable clinical

manifestations. Asthma is no longer considered a single disease, being of interest
to identify the phenotype, based on the association of clinical manifestations,
respectively the endotype, based on the main pathogenic mechanisms involved
in the genesis of airway inflammation and remodeling. Determining asthma
phenotype and endotype is essential for implementing personalized therapy. This
need is more important in patients with severe and difficult to control asthma, who
consume more than 50% of the health system resources allocated to asthmatics
and have an increased risk of mortality. Severe asthma in children is complex,
and patients should be well investigated in order to confirm the diagnosis and
to initiate the best treatment strategy, which could include biologics. There are
two biologics approved as add-on therapy in asthmatic children aged at least
6 years: anti-IgE (Omalizumab) for uncontrolled moderate to severe persistent
allergic asthma, and anti-IL5 (Nucala) for severe refractory eosinophilic asthma.
Dupilumab, which inhibits IL-4 and IL-13 signalling, is indicated in children aged
12 years and older with moderate-to-severe asthma with eosinophilic phenotype
or with oral corticosteroid dependent asthma. The heterogeneity of biological
markers and asthma phenotypes, together with the potential overlap of several
phenotypes and/or endotypes in a single patient, contribute to the difficulty of
precisely defining them. This supports the need for studies on larger groups of
patients, using advanced statistical techniques for data interpretation.
Acknowledgement: Supported by INSPIRED project (SMIS 103663)

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PROBIOTICS AND ATOPIC DERMATITIS

PROPHYLAXIS
Diana Deleanu, Irena Nedelea
UMF “Iuliu Hatieganu”, IRGH- Alergologie, Cluj-Napoca, Romania
Probiotics (ProB) are on research in the last years for their immunomodulatory
effects. In 1965, Lilly and Stillwell described ProB as microorganisms stimulating
the growth of other microorganisms.
ProB are defined as live harmless microorganisms for humans. Different
bacteria belonging to the geni Lactobacillus, Bifidobacterium, and Lactococus,
Streptococcus, Enterococcus are used as human ProB. Also strains of Gram-
positive bacteria Bacillus and some yeast strains as Saccharomyces are used in
ProB products. Atopic dermatitis (AD) is becoming more frequent in the last
years, reaching 8-20% prevalence. AD is one of the first manifestation of allergy
and also is a risk to develop asthma. It is assumed that in AD, early microbial
stimulation contributes to the deregulation of immune system. That hypothesis
led the idea of ProB use in the prevention and treatment of AD.
Meta-analysis were published with some benefits of ProB in the prevention of
AD. In two RCTs, infants at high risk for atopy who received ProB developed AD
significantly less frequently during the first 2 years of life. Their mothers received
Lactobacillus rhamnosus GG with or without other ProB perinatally, followed by
treatment of the infants with the same ProB during 6 months. But in another
trial, neither the frequency nor the severity of AD during the first year of life
were different between active and control group infants. No effect is observed
in development of asthma. In conclusion it is needed more studies to elucidate
whether ProB are useful for the treatment or prevention of AD.

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PRIMARY ANTIBODY DEFICIENCY

– EPIDEMIOLOGY, CLINICAL FEATURES
AND EARLY DETECTION
Irena Nedelea1,2, Diana Deleanu1,2,3

1
Allergy Department, Professor Doctor Octavian Fodor RIGH,
Cluj-Napoca, Romania; 2Allergology and Immunology Discipline, “Iuliu
Hatieganu” UMF, Cluj-Napoca, Romania; 3Internal Medicine Department,
Professor Doctor Octavian Fodor RIGH, Cluj-Napoca, Romania
In this paper, we aim to approach the topic of primary antibody

immunodeficiency from the perspective of epidemiology, clinical features,
and early detection. According to the estimates of the European Society for
Immunedeficiences, primary immunodeficiency diseases encompass 330 intrinsic
defects of immunity, most of which are inheritable, with 320 genetic mutations
being identified. As per data reported by 125 European centers, approximately
20.000 individuals suffer from primary immunodeficiency, while almost 6 million
people suffer from a form of primary immunodeficiency worldwide. Moreover,
70-90% of primary immunodeficiencies remain undiagnosed. The presence of an
underlying primary humoral immunodeficiency should be suspected in a patient
with severe recurrent invasive infections, caused by unusual or opportunist
pathogens, which respond poorly to standard treatment, require prolonged
parenteral therapy. In infants, a classic presentation for primary humoral
immunodeficiency consists of a susceptibility to infections which arises at four to
nine months of age, when protective levels of the maternal antibodies have faded.
Newborn screening for severe B cell deficiencies is possible by measurement
of kappa-deleting recombination excision circles (KRECs) levels in blood and in
DNA isolated from dried blood spots (DBS). KRECs are undetectable in primary
immunodeficiencies in which B cells are absent or dysfunctional. This screening
is under investigation in several countries and states in the US. Early diagnosis is
essential for affected individuals.

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AWARENESS OF REPORTING ATOPIC

DERMATITE PHENOTYPES
Carina Petricău1,2, Irena Nedelea1,3, Diana Deleanu1,2,3

1
Allergy Department, “Professor Doctor Octavian Fodor” Regional Institute
of Gastroenterology and Hepatology, Cluj-Napoca, Romania
2
Internal Medicine Department, “Professor Doctor Octavian Fodor”
Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca,
Romania; 3Allergology and Immunology Discipline, “Iuliu Hatieganu”
University of Medicine and Pharmacy, Cluj-Napoca, Romania
An estimated 10 to 30% of children worldwide have atopic dermatitis (AD).

Despite it’s name, AD, is not considered an allergic reaction but rather a chronic,
intensely pruritic, inflammatory skin condition that affects sleep and quality of
life. Controversy with regard to the role of allergic sensitization in AD continues,
however the strong association with other atopic comorbidities cannot be
ignored, supporting the atopic march hypothesis. Recently, several studies have
defined various phenotypes of atopic dermatitis depending on the onset and
persistence of symptoms, thereafter evaluating the risk to develop other allergic
disorders. The early transient phenotype represents the short-lived presence of
AD which is associated with the increased risk for food allergy during childhood.
The early persistent phenotype of AD is correlated with a family history of atopy,
persistent food allergy and significant risk to develop allergic rhino conjunctivitis
and allergic asthma. The late phenotype with onset of AD after 2 years of age
is linked to development of allergic rhinitis in childhood. Sensitization to food
and inhalant allergens is reported to be the highest among the early persistent
phenotype, making them vulnerable to other atopic conditions at later ages.
Since uncontrolled AD can lead to sensitization through a disrupted skin barrier
and subsequently serious allergic disease, our focus should be on prevention in
the early persistent phenotype.

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THE ROLE OF VITAMIN D RECEIVER

POLYMORPHISMS IN MELANOMA
AND CUTANATE CARCINOAMES
Simona Șenilă1, Alina Vasilovici1, Loredana Ungureanu1,

Elisabeta Candrea1, Sorina Dănescu1, Rodica Cosgarea1
1
Clinica Dermatologie, UMF “Iuliu Hațieganu” Cluj-Napoca, Romania
Melanoma represents the most aggressive skin cancer, with an unpredictable

and often treatment resistant behavior. The etiology of melanoma is multifactorial
and includes both environmental and genetic factors. Recent evidence indicates
that vitamin D has a role in the development and progression of melanoma.
The biologically active form of vitamin D/1,25-dihydroxyvitamin D3 acts by
binding to a intranuclear receptor: vitamin D receptor (VDR). Single nucleotide
polymorphisms (SNPs) in the vitamin D receptor gene may alter the expression or
the function of the VDR protein leading to various diseases, including melanoma.
More than 600 SNPs have been identified in the VDR gene, but only a few have
been analyzed in relation to melanoma risk: FokI, TaqI, BsmI, ApaI, Cdx2, EcoRV, and
BglI. Individual studies carried on small cohorts of patients reported controversial
results. In an attempt to clarify the available data in the literature on this subject,
we elaborated a systematic review in which we analyzed the relationship between
VDR gene polymorphisms and melanoma risk and progression. We concluded
that vitamin D pathway is important for the pathogenesis and the progression
of cutaneous melanoma, illustrating the gene-environment interactions, but
well-designed prospective studies that include data on both genotypes and
phenotypes of vitamin D metabolism are essential in order to understand the
mechanisms underlying the association between vitamin D and melanoma. We
will present the results of this systematic review and the new data about the role
of vitamin D receptor gene polymorphisms in development, progression and risk
of non-melanoma skin tumors.

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BACTERIAL BIOFILMS IN DERMATOLOGIC

DISEASES
Mara Mădălina Mihai1,2, Mădălina Maria Muntean3,4, Mădălina Preda4,5,

Alexandru Andrei Muntean4, Mircea Ioan Popa3,4
1
Oncologic Dermatology Department - “Elias” Emergency University
Hospital, “Carol Davila” University of Medicine and Pharmacy, Bucharest;
2
Dermatology and Allergology Clinic, “Elias” Emergency University
Hospital, Bucharest; 3Microbiology Department 2, “Carol Davila” University
of Medicine and Pharmacy, Bucharest; 4“Cantacuzino” National
Medico-Military Institute for Research and Development, Bucharest;
5
Microbiology, Parasitology and Virology Department, “Carol Davila”
University of Medicine and Pharmacy, Bucharest.
The most frequent dermatologic diseases are chronic inflammatory disorders.

Atopic dermatitis, acne, chronic folliculitis and furunculosis, non-healing wounds,
the follicular occlusion tetrad (folliculitis decalvans, hidradenittis suppurativa,
acne conglobata, pilonidal sinus) and others represent a major public health
burden worldwide.
While the ethiopathogenesis is multifactorial involving genetic, external and
internal factors, chronic microbial colonisation or infection are almost constantly
present, raising the hypothesis of their crucial involvement in disease chronicity.
Bacterial biofilms are complex poly-microbial communities, characterized by
tolerance to antibiotics and to host immune defense mechanisms, attributes
sufficient to cause chronic infections and trigger a low-grade inflammatory
response of the host.
They have been intensely studied in human pathologies such as periodontal
disease, device-related infections, but also in the area of dermatology, especially
in chronic wounds. In this presentation we aim to review the implication of
bacterial biofilms in the pathogenesis of dermatological diseases, with a focus
on non-healing wounds.

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PEDIATRIC MASTOCYTOSIS
– CLINICAL PROGRESS AND MANAGEMENT
Elena Camelia Berghea
„Carol Davila” University of Medicine and Pharmacy, Bucharest
Mastocytosis is characterized by expansion of clonal mast cells in different

organs, often related to activating KIT mutations. Cutaneous mastocytosis is
characterized by a pathologic accumulation of mast cells in theskin, without
histologically involvement of other organs in the majority of pediatric patients.
Clinical presentation varies from a solitary plaque to widespread cutaneous
disease, classified as maculopapular cutaneous mastocytosis (MPCM), also
known as urticaria pigmentosa (UP), solitary mastocytoma, or, less commonly,
diffuse cutaneous mastocytosis (DCM).
Symptoms are triggered by mast cell degranulation. In the pediatric
population, spontaneous remission is typical, generally by puberty, and ther isk
of anaphylactic reactions correlates withth eseverity of skin involvement and the
serumtryptase level. Important to know, serumtryptaselevels are usually within
the normal range, but in some cases with pronounced cutaneouslesions, tryptase
level could be increased at diagnosis but usually decreas ewithin 1 to 2 years. It
is therefore important to adapte diagnostic approaches and the management of
cutaneous mastocytos is to the pediatric population.

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MANAGEMENT OF THE LEG

CHRONIC VENOUS DISEASE
G. Ianoși, Simona Ianoși, L. Drăgușin, G. Gîngeoveanu, Daniela Neagoe
Medical Center Dr. Ianoși Craiova, Romania
Chronic venous disease of the leg affects, related to some studies, half of
the population an one third of the active peoples. The disease’s management is
not completely establish caused by widely extension of the disease and multiple
pathophysiological mechanisms. The treatament addresses to the stage of the
disease.
There are many treatment methods that were suggested for this disease. In
this paper we want to present a large variety of treatments for chronic venous
disease of lower limbs basing on our experience but also using data from
literature. We presented treatment methods related to CEAP stadialization with
it’s last completions.
In this field we will discuss about prophylaxy, venoactive drugs, compressive
therapy, wound and skin care, but also about invasive treatments: different types
of sclerotherapy, endovenous ablative therapy (laser, radiofrequency, mecano-
chemical, thermal etc.), endovenous deep system therapy, surgical therapy
(surgical for truncal vein or venous tributaries, valve reconstruction, perforator
vein surgery). A separate chapter involve aesthetic treatments for telangiectasias
or scars.

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CYTOKINE AND CELL ADHESION MOLECULES,

THEIR IMPORTANCE IN PATHOLOGY
(PERSONAL EXPERIENCE)
Victor Cristea, Nicolae Miron (Sweden), Ona Livia (Germany),

Irene Nedelea, Elena Tâlvan
UMF “Iuliu Hațieganu”, Cluj-Napoca
The discovery, more than 45 years ago, of the first molecules involved in
modulating the immune response, brought some clarification on the intimate
mechanisms of cell signaling and cooperation. Throughout those years new
soluble factors have been discovered having different roles and effects.
As often had happened in immunology, when the information explosion had
not found enough time for the recent acquisitions to settle, to be understood and
systematized (see HLA, CD, genetics of Ig), the study of those mediators continue
today simultaneously in several directions with clarifications and confusion in
equal measure. Justly, the researcher who tries to grub up the multitude of data
that had accumulated, experiences the same feelings as an unsuspecting hiker
that suddenly enters into a “zoo of factors, jungle of interactions, swamp of
acronyms or desert of synonyms” (J.A. Symons, 1995).
In the following we will briefly expose our own view on these mediators, a
classification that we assume and that has as its starting point the molecular
criterion beyond the clinical or the therapeutic one.

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DUPILUMAB: A NEW STANDARD

IN THE TREATMENT OF MODERATE
TO SEVERE ATOPIC DERMATITIS
Daniel Boda
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
Atopic Dermatitis (AD) is a serious disease affecting both children and adults.
AD is a chronic systemic inflammatory disease and not only an intermittent skin
disease as previously thought. Non-lesional (normal looking) skin is not normal
skin due to a persistent underlying inflammation. IL 4 and IL13, as part of the
Type 2/Th2 pathway, are key cytokines in AD pathophysiology.
Dupilumab is the first therapy in AD that provides continuous, long term and
safe disease control by targeting 2 key cytokines of underlying inflammation.
Unique mechanism of action that inhibits the dual signaling of IL4 and IL13.
Consistent, rapid and sustained long term efficacy on signs and symptoms, as
seen on lesion extent and severity pruritus intensity, quality of life, including sleep,
anxiety and depression. Strong safety and tolerability profile with an overall rate
of adverse events comparable to placebo and no laboratory monitoring required.

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VIRAL VERSUS DRUG

INDUCED EXANTHEMA
Selda Ali1,2, Roxana Silvia Bumbacea1,2

1
.“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
2
. Department of Allergology, “Dr. Carol Davila” Nephrology Clinical
Hospital, Bucharest, Romania
Morbiliform eruptions are frequently caused by either viral infections or

drug treatments. They tend to be diffuse and symmetric, with the majority of
the eruptions presenting as isolated, blanching erythematous macules or small
papules on the trunk and proximal extremities. Drug-induced exanthemas, also
called maculopapular or morbilliform drug eruption, are the most common
cutaneous reactions to drugs, responsible for approximately 95 percent of all
drug rashes. The mucosae (anogenital, oral, conjunctival or nasal) and skin
appendages (nails, hair) may be involved in severe forms.
Viral exanthemas may represent a reaction to a toxin produced by the
organism or an immune response. It is believed that associated viral infections
may predispose vulnerable individuals to develop an allergic morbilliform drug
eruption. Viral exanthems are often self-limited and treatment is supportive,
while morbilliform drug induced eruption needs a different management.
A maculopapular drug eruption is difficult to differentiate from viral exanthema,
especially when a patient with a viral infection has been prescribed drugs that
may trigger a rash.

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TOLL-LIKE RECEPTOR
IN PSORIASIS PATHOGENY
Mihail Alecu1,2, Gabriela Coman1, Alina Muşetescu1,2,

Oana Andreia Coman1,3
1
Dermatology Department, “Dr. Victor Babeş” Hospital for Infectious and
Tropical Diseases, Bucharest;
2
Faculty of Medicine, “Titu Maiorescu” University, Bucharest;
3
University of Medicine and Pharmacy “Carol Davila” Bucharest, Romania.
Innate immunity is now considered an important component of the pathogenic

processes, both of those with immune mechanism and those with a reduced
immunological component. TLR (Toll-like receptor) are a family of transmembrane
proteins that recognize molecular patterns on the surface of pathogens (PAMP-
Pathogen Associated Molecular Pattern). Coupling of TLR with PAMP ligands
molecules has the effect of activating the adaptor proteins, transcription factors
and increasing the cytokine secretion by TLR expressing cells. TLR expression on
numerous cell types, including keratinocytes, and activation of TLR molecules
by several substances, not only microbial components, opens new perspectives
for understanding the pathogenic mechanisms of multiple diseases, including
psoriasis.
Psoriasis is a disease in which T cells and proinflammatory cytokines play a
key role, accelerating the process of terminal differentiation of keratinocytes.
TLR activation increases the release of proinflammatory cytokines, antimicrobial
peptides, and is involved in activation of the IL-23 / IL-17 axis. Co-morbidities
found in psoriasis are explained largely by increased secretion of pro-inflammatory
cytokines mediated by the TLR.

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PITYRIAZIS RUBRA PARANEOPLAZICA

PILAR (PRP): CASE PRESENTATION
AND LITERATURE REVIEW
Fekete Gyula László1, Daniel Boda2, Constantin Căruntu2, Fekete László3
1
University of Medicine and Pharmacy, Dermatology Clinic, Târgu Mureş,
Romania; 2“Carol Davila” University of Medicine and Pharmacy, Bucharest,
Romania; 3CMI Dermamed Târgu Mureş, Romania.
Pityriasis rubra pilaris (PRP) is a chronic papulo-squamous disorder of

unknown etiology characterized by reddish orange scaly plaques, islands of
sparing, palmoplantar keratoderma, and keratotic follicular papules.
Cases of PRP associated with malignancy are unusual. We present a case of a
58-year-old man, with the tipical clinical aspect of PRP with an onset of the disease
of four months. The histopathologyc and dermatoscopic fiindings confirmed
the diagnosis of PRP. Routine laboratory results were in normal limits excepting
the number of eosinophils which was elevated and the number of lymphocytes
which was lower. The hematologyc consulting after a thorough examination
cannot conclude about the cause of hypereosinophilia. We performed imagistic
examination and we found only a prostate hypertrophy. We have examined
the prostate-specific antigen (PSA) level, which was increased. The urologic
consultation diagnosed a prostate carcinoma on early stage. Our final conclusion
was a paraneoplastic PRP in association with prostate carcinoma. We searched in
international databases and found twelve published cases about the association
of PRP with malignancies. Our presented case represents a rare coexistence of
PRP with malignancy, particullary with prostate carcinoma, and indicates that
PRP can occur as paraneoplastic dermatosis, heralding a malignancy. Our case
is the first case that present PRP associated with prostate carcinoma. Anyway,
we suggest that PRP can be considered a paraneoplastic syndrome, so tumor
screening must be mandatory in cases presenting this disease.

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EXCIMER LASER IN THE TREATMENT

OF PSORIASIS - CASE PRESENTATION
AND LITERATURE REVIEW
Valeriu Ardeleanu1,2,3,4, Diana Sabina Radaschin4,5,6,

Florin Ciprian Bujoreanu4,6, Alin Laurențiu Tatu4,5,6
1
Arestetic Clinic Galați;
2
Faculty of Medicine, Ovidius University from Constanța;
3
General Hospital CFR Galați, Surgery Department; 4“Dunărea de Jos”
University form Galați, Romania; 5Faculty of Medicine and Pharmacy,
Pharmacology Sciences Department, Dermatology; 6Infectious Disease
Hospital “St. Parascheva” Galati, Romania.
Psoriasis is a common cutaneous disease that has major implications in the

quality of life of the patient. It is characterised by a chronic course and in some
subtypes, it can be life threatening.
Many studies focused on the pathogenesis concerning this disease therefore
improving the therapeutic approaches. Phototherapy represents a well-known
treatment option for psoriasis.
The depletion of T cells mostly from the epidermis, after exposing to
phototherapy, validates the role of this treatment. The 308 nm excimer laser
has the ability to treat mild, moderate and even severe but localised psoriasis
plaques and plays an important role in the treatment management of psoriasis.
In this paper, we present the case of a patient diagnosed with plaques psoriasis,
resistant to topical ointments, successfully treated with the 308 nm excimer laser.
Even though further studies are required to consider the 308nm excimer
laser a first line therapy, its high response rates have significantly influenced the
therapeutic approach in psoriasis.

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PSORIASIS - NEW DATA ON EPIDEMIOLOGY

AND RISK FACTORS
Simona Ianoși, Daniela Neagoe, Gabriel Ianoși
Medical Center Dr. Ianoși Craiova, Romania
Psoriasis is an immune disorder of the skin and joints with a negative impact
on the physical, emotional and psychosocial wellbeing of affected patients.
Although psoriasis occurs worldwide, its prevalence varies considerably.
Psoriasis is found worldwide but the prevalence varies among different ethnic
groups. It has a strong genetic component but environmental factors such as
infections, smoke, alcohol consumption, some drugs, stress, infections, pregnancy,
vitamin D deficiency etc. can play an important role in the pathogenesis.
The epidemiology, the role of each environmental factors involved in psoriasis
is reviewed.

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NEW TRENDS IN DERMATOLOGICAL RESEARCH

– ALTERNATIVE NON-ANIMAL METHODS
Cristina Dehelean
Facultatea de Farmacie, Universitatea de Medicină şi Farmacie

“Victor Babeş”, Timişoara
The ethical pursuits regarding the use of animals in research determined

the development of different alternative methods that rely on the 3Rs principle
(Refinement, Reduction and Replacement). The dermatology research field is
directly affected by these regulations, since the animal tests are prohibited in
cosmetic research.
Due to the numerous drawbacks of animal experimentation (high cost,
improved quality and precision of the data, genetic variability), these methods
were replaced by alternative non-animal-based techniques, as: biochemical tests,
2D and 3D cell cultures, genome-based studies, in silico computer simulations
of skin models and volunteer assays (non-invasive techniques). At present, a
considerable number of alternative methods for skin sensitization, skin corrosion
and eye irritation were adopted by OECD (Organization for Economic Co-ope-
ration and Development), still each method has its limitations. Another recent
approach proposed to elucidate the target proteins and mechanism of disease
(autoimmune blistering skin diseases, atopic eczema) in dermatology is the use
of mass spectrometry.
The variety of the alternative non-animal-based methods increases
researchers accessibility and compliance, and also, the quality of results, still a
well-documented screening for choosing the suitable method is recommended.

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MEDICINA PERSONALIZATĂ ÎN CABINETUL

MEDICULUI DE FAMILIE
Dr. Adriana Mihălaș
Centrul Medical de Diagnostic, Tratament Ambulator și Medicină
Preventivă, București
CORELAȚII CLINICE ȘI IMUNOLOGICE ÎN

ALERGIA LA PROTEINA DIN LAPTELE DE VACĂ
Prof. Univ. Dr. Coriolan Emil Ulmeanu¹, Viorela Gabriela Nițescu²
¹UMF „Carol Davila” București; ²SCUC „Grigore Alexandrescu”, București
PARTICULARITĂȚI ALE EXANTEMELOR

MACULO-PAPULOASE LA COPII
EVALUAREA ALERGOLOGICĂ A EXANTEMELOR

MACULO-PAPULOASE
Conf. Univ. Dr. Roxana Silvia Bumbăcea
Președinte Societatea Română de Alergologie şi Imunologie Clinică
(SRAIC); Șef Disciplină Alergologie, UMF „Carol Davila”, București;
Spitalul Clinic de Nefrologie “Dr. Carol Davila”, București

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ABSTRACTE
SÂMBĂTĂ, 21 SEPTEMBRIE 2019
Workshop: „Imunodiagnosticul și imunoterapia

melanomului și altor tumori cutanate”
- organizat în cadrul Proiectului
PN-III-P1-1.2-PCCDI-2017-0341 PATHDERM

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EPITHELIAL-MESENCHYMAL TRANSITION
PECULIARITIES IN MELANOCYTIC NEVI WITH
TUMOR VASCULAR PROTRUSION
Oana Stefan1*, Georgiana-Irina Tudor1*, Corina Constantinescu1,

Cristina Luca1, Daniel Boda2, Constantin Caruntu2, Virginia Chitu1,2,
Cristiana Popp1, Alexandra Cioroianu1,2, Mirela Cioplea1,
Luciana Nichita1,2, Sabina Zurac1,2
1
Colentina Clinical Hospital, Bucharest;
2
“Carol Davila” University of Medicine and Pharmacy; Bucharest, Romania.
Common melanocytic nevi are benign skin tumors composed of melanocytes.

Histopathologically, they may rarely exhibit tumor vascular protrusion, either as intravascular
nevus cell protrusions or intravascular nevus cell aggregates. Since vascular invasion is a
prerequisite for metastasis occurrence and epithelial–mesenchymal transition (EMT) is one
of the main process involved in metastatic progression we decided to analyze E-cadherin and
N-cadherin expressions in common melanocytic nevi with and without vascular protrusion.
We have conducted a case-control study by randomly choosing 30 melanocytic
nevi with vascular protrusion diagnosed between 2017-2018 in our department and by
matching them individually by age, sex and anatomical location of the lesion with 30 nevi
that do not express this histopathological feature, thus forming the study and the control
groups. Immunohistochemistry for E-cadherin and N-cadherin using a red chromogen
was performed. In both study and control groups, we have found that E- and N-cadherin
have up to seven patterns of expression: superficial, deep, mostly superficial, mostly deep,
overall, patchy, and negative. We identified statistically significant tendency towards deeper
patterns of E-cadherin expression and towards the complete loss of this adhesion molecule
within nevi with intravascular growth, with an odds ratio of 3.5 and a p-value of 0.037.
The N-cadherin immunohistochemical tests did not reveal statistically significant
differences in expression patterns between these two groups.
Common melanocytic nevi with vascular protrusion have predilection for certain
E-cadherin patterns of expression but its significance is still to be debated. Further studies
in the with larger sample size for additional statistical power are needed.
Acknowledgement: *O. Stefan and G.I. Tudor equally contributed to this work. This
work was supported by a grant of Romanian-Ministry-of-Research-and-Innovation, CCCDI-
UEFISCDI, project number 61PCCDI⁄2018PN-III-P1-1.2-PCCDI-2017-0341.

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DOPACHROMETAUTOMERASE IS A NOVEL
REGULATOR OF STRESS RESISTANCE
PATHWAYS IN MELANOMA
Anca Filimon, Teodora Grigore, Adina Dobre, Gabriela Negroiu
Department of Molecular Cell Biology, Institute of Biochemistry

of Romanian Academy, Bucharest, Romania
Cutaneous melanoma is characterized by insidious and fast progression,

heterogenic evolutions and significant resistance to numerous therapeutic strategies.
Dopachrometautomerase (DCT) is a member of Tyrosinase Related Protein family,
melanogenetic enzyme, melanoma antigen and more recently an important player in
pathways regulating environmental and therapeutic stress in normal and transformed cell
phenotypes. Amino acid stress resistance (AAR) involves activation of complex, multiple
mechanisms as shifting the resources and enegry to synthesis of growth hormones,
membrane transporters, protein recycling, triggering autophagy. Two ubiquitous AA-
sensing processes have been described up to now in mammals. One involves mTORC1
activated by AA supplementation and other GCN2 activated by AA starvation. Despite the
intense studies of both pathways the regulatory mechanisms of principal genes involved
are not yet identified.
We present here, for the first time, experimental evidence that DCT is a new player
involved in modulation of AAR in melanoma. A well known regulator of cell stress
mechanisms in tumor biology, acting in GCN2 branch of AAR has been identified as target
of DCT in a human melanoma cell line. Additional data indicate that DCT is involved also in
regulating ER stress mechanisms by altering expression of a chaperone needed for protein
folding, including essential components of ECM. Importantly, ECM integrity is required for
tumor migration and invasion processes. Further studies aim to dissect DCT impact on other
participants of both AAR- and ER-stress pathways.
These new data introduce DCT as a novel, specific regulator of stress mechanisms in
melanoma and a potential therapeutic target.
Acknowledgements: This work was supported by Grant Application no 61-PCCDI-2018,
National Programe PN-III-P1-1.2 PCCDI-2017, funded by Ministry of Education and Scientific
Research.

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ASSOCIATION OF DERMATOMYOSITIS
WITH MALIGNACY
Emilia Manole1,2, Gisela Găină1,3, Alexandra Bastian4,5

1
Colentina Clinical Hospital, Pathology Department, Research Center,

2
Bucharest, Romania; 3Department of Biochemistry and Molecular

Biology, University of Bucharest, Romania; 4“Carol Davila” University of
Medicine and Pharmacy, Bucharest, Romania; 5Colentina Clinical Hospital,
Pathology Department, Bucharest, Romania.
Dermatomyositis (DM) is a multifactorial chronic autoimmune disorder with

characteristic skin changes and involvement of different organ systems: muscles, blood
vessels, joints, esophagus, lungs. DM affects both children and adults. It is also regarded
as a paraneoplastic phenomenon, ascancer may precede, occur concurrently with, or
follow the development of the clinical signs. The cutaneous manifestations of DM can
be categorized as pathognomonic, characteristic, compatible, less common, rare, recent,
and nonspecific. Many patients with DM have circulating autoantibodies, which are often
associated with distinct clinical phenotypes.
Autoantibodies in DM tend to be mutually exclusive, suggesting that specific immune
responses might play a role in shaping different phenotypes. There are DM patients at
increased risk of internal malignancy around the time of DM diagnosis. Identification
of patients at high risk of cancer remains a high priority for physicians treating these
patients. The molecular mechanisms underlying this association are not fully understood.
Treatment and factors that predict associated cancer and its prognosis all remain unclear.
Recent studies have shown an increased cancer risk in male patients with DM who are
older than 50 years.
The early discovery of malignancy is critical in cases of DM. The treatment of DM
is a difficult task due to its rarity, its multiple phenotypes, and the fact that the disease
may affect multiple organs and is commonly treatment-refractory. In this presentation
we review the most recent studies regarding the relationship between DM and different
types of cancer, as well as new autoantibody specificities in DM.

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WNT 5A SIGNALING PATHWAY

IN THE DERMATOLOGIC PATHOLOGY
Robert Ancuceanu1, Mihaela Dinu1,

Adriana Iuliana Anghel1, Daniel Boda2
1
“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy,
Pharmaceutical Botany and Cell and Molecular Biology Department,
020956, Bucharest, Romania;
2
Dermatology Research Laboratory, Carol Davila University of Medicine
and Pharmacy, 050474 Bucharest, Romania.
Wnt5a is one of the 19 members of the Wnt family of secreted glycoproteins,

which are classified into canonical or noncanonical ligands, based on the involvement
of the β-catenin in the signaling pathway (canonical signaling) or the absence of
β-catenin from the signaling pathway (non-canonical signaling). Wnt ligands are
known to bind to the Frizzled receptors (10 members known currently), as well as to
a number of co-receptors (e.g. LRP-5/6, Ryk, Ror2).
The Wnt receptors are also classified into canonical or noncanonical, based on the
same criterion. Wnt5a has been typically considered as involved in the non-canonical
signaling, although it was later shown that it is able to activate beta-catenin signaling.
Wnt5a signaling might be involved in a complex way in psoriasis.
Its canonical signaling has been suggested to be involved in melanocytes
differentiation and thus, relevant for vitiligo, as well as in the outer root sheath cells
under the influence of light-emitting diodes.
Wnt5a is proposed to be involved in the pathology of different cancers, although
its role has also not been easily pinned down; in melanoma, its overexpression is
suggested to be part of an “invasive signature”.

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IN VIVO VIRTUAL BIOPSY

OF SKIN CANCER
Constantin Căruntu1,2, Mihai Lupu1, Mihaela Adriana Ilie1,

Ana Caruntu3,4, Daniel Boda1, Sabina Zurac1,5, Carolina Constantin5,6,
Monica Neagu5,6,7

1
2
“Prof. N.C. Paulescu” NIDNMD, Bucharest, Romania;
3
“Titu Maiorescu” University, Faculty of Medicine, Bucharest, Romania;
4
“Carol Davila” Central Military Emergency Hospital, Bucharest, Romania;
5
Colentina Clinical Hospital, Bucharest, Romania;
6
7
In vivo confocal microscopy is one of the most promising noninvasive imaging

techniques for evaluation of skin tumors. Using this device, the structure of skin
lesions can be visualized with a resolution close to conventional histopathology, thus
enabling us to perform a virtual skin “biopsy”. We will present the experience of our
group in microstructural evaluation of the most common malignant skin tumors using
in vivo confocal microscopy, as well as future possible applications of this technique
in experimental dermato-oncology studies.
This study was partially funded by a grant of the Romanian Ministry of Research
and Innovation (CCCDI-UEFISCDI; project no. 61PCCDI⁄2018 PN-III-P1-1.2-
PCCDI-2017-0341), within PNCDI-III.

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UVEAL MALIGNANT MELANOMA

IN THE XXI ST CENTURY - OPTIONS AND
LIMITS IN OUR DAILY PRACTICE
Horia T. Stanca1,2, Bogdana Tăbăcaru1,2, Ciprian Maftei2,

Monica Mălăescu2, Alina Lazăr2
1
“Carol Davila” University of Medicine and Pharmacy,
Ophthalmology Department;
2
“Prof. Dr. Agrippa Ionescu” Clinical Emergency Hospital,
Eye Clinic, Bucharest, Romania.
While uveal melanoma represents only 5% of all melanomas, it is the most

common primary intraocular malignancy of the adult eye. Uveal melanomas arise
from melanocytes within the uveal tract. Choroidal melanomas, the most common
ocular melanoma, result not only in vision loss, but also in metastasis, which is
uniformly fatal. Current treatment for local disease, including eye-sparing approaches
(e.g., radioactive plaque therapy, external beam radiation, laser therapy), often leads
to profound loss of vision. Unfortunately, despite advances in the diagnosis and
treatment of the primary tumor, we have not witnessed a corresponding improvement
in patient survival.
Metastases most commonly target the liver, and the detection of hepatic metastatic
lesions predicts a dismal outcome, with a median survival of only a few months. The
high rate of metastasis in patients diagnosed with uveal melanoma despite local
treatment is thought to be due to the presence of micrometastases that occur prior
to diagnosis and treatment. These micrometastases can remain dormant, often for
years or decades, before manifesting clinically as metastatic disease.
It is therefore essential that we identify patients at risk for metastasis early, so that
we may provide adjuvant systemic therapy in an effort to delay or perhaps prevent
the progression to clinical metastatic disease. Our paper presents the nowadays
knowledge about uveal malignant melanomas corroborated with some clinical cases
from our daily practice.

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PARTICULARITIES OF EPITHELIAL
MESENCHYMAL TRANSITION
IN CUTANEOUS MELANOMA
Gabriela Turcu1,2,3, Anastasia Coman1,2, Roxana Ioana Nedelcu1,3,4,

Alice Brînzea1,4, Andreea Moroianu1,3, Mihaela Antohe1,3, Mihaela
Bălăban1,3, Cătălin Mihai Popescu1,2, Raluca Popescu1,2, Cristiana Popp5,
Mirela Cioplea5, Luciana Nichita1,5, Ionela Hulea1, Ioana Anca Bădărau1,
Daniela Adriana Ion1,4
1
2
Dermatology Department I, Colentina Clinical Hospital, Bucharest,
Romania; 3Derma 360° Clinic, 011273 Bucharest, Romania; 4National
Institute for Infectious Diseases Prof. “Dr. Matei Balș”, Bucharest, Romania;
5
Pathology Department, Colentina Clinical Hospital, Bucharest, Romania.
Epithelial–mesenchymal transition (EMT) is an essential process involved in

the progression of epithelial cancers to metastatic disease. It implicates several
mechanisms such as activation of transcription factors, altered expression of
specific cell-surface proteins, reorganization and expression of cytoskeletal proteins,
production of extracellular matrix-degrading enzymes and changes in the expression
of specific micro RNAs.
Due to their neuroectodermal origin, normal melanocytes express some EMT
markers so that melanoma cells do not undergo classic EMT-like modifications.
The impredictible and aggressive evolution of melanoma is in part explained by
the presence of these predisposing intrinsic factors and by context dependent
interchange between epithelial-like and mesenchymal-like phenotypes.
We will highlight the particularities of EMT in melanoma that support the idea that
EMT is a polymorphic and distinct phenomenon with elements characteristic to each
type of tumor.
Acknowledgement: This work is supported by grants of Ministery of Research
and Innovation, CNCS-UEFISCDI, project number PN-III-P4-ID-PCE-2016-0641,
within PNCDI III and CCCDI-UEFISCDI, project number 61PCCDI⁄2018 PN-III-P1-1.2-
PCCDI-2017-0341, within PNCDI-III.

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PARTICULARITIES OF EPITHELIAL
MESENCHYMAL TRANSITION IN CUTANEOUS
SQUAMOUS CELL CARCINOMA (CSCC)
Roxana Ioana Nedelcu1,2, Andreea Moroianu1,2, Alice Brînzea1,4,
Gabriela Turcu1,2,3, Anastasia Coman1,3, Mihaela Antohe1,2,
Mihaela Bălăban1,2, Cătălin Mihai Popescu1,3, Raluca Popescu1,3,
Cristiana Popp5, Mirela Cioplea5, Luciana Nichita1,5, Ionela Hulea1,
Ioana Anca Bădărau1, Daniela Adriana Ion1, Sabina Andrada Zurac1,5
1
2
Derma 360° Clinic, 011273 Bucharest, Romania; 3Dermatology
Department I, Colentina Clinical Hospital, Bucharest, Romania;
4
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”,
Bucharest, Romania; 5Pathology Department, “Colentina Clinical”
Hospital, Bucharest, Romania.
Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin
cancer. cSCC could be easily treated with a high cure rate in early stages, while it has
poor prognosis if it invades lymph nodes and anatomically distant sites. Accurate clinical,
histological and immunohistochemical correlations can identify biomarkers involved in
the development and evolution of this malignancy and reveal an appropriate personalized
treatment. In this presentation, we have focused on the involvement of epithelial-
mesenchymal transition (EMT) in cSCC mechanisms. Different authors have analyzed
the role of EMT in cutaneous squamous cell carcinogenesis, using human and animal
models, studying the expression and activity of epithelial and mesenchymal markers,
transcription regulatory factors, relevant intra and extracellular pathways. Summarizing,
EMT in the setting of cSCC is a process far from being completely understood. The process
has been explained through two important aspects in the cSCCs metastases process: the
loss of the expression of epithelial markers in order to invade and disseminate from the
primary tumor; the need to revert to an epithelial identity in order to form metastases
to distant sites. This hypothesis could have major implication for the management of
cSCC, questioning whether therapeutic agents that inhibit EMT or therapeutic agents that
inhibit the reversion of EMT would be more appropriate to be used as a treatment.
Acknowledgement: This work is supported by grants of Ministery of Research and
Innovation, CNCS-UEFISCDI, project number PN-III-P4-ID-PCE-2016-0641, within PNCDI
III and CCCDI-UEFISCDI, project number 61PCCDI⁄2018 PN-III-P1-1.2-PCCDI-2017-0341,
within PNCDI-III.

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ROLUL ARN-URILOR NONCODIFICATOARE

ÎN PATOLOGIA TUMORALĂ.
OPORTUNITĂȚI TERAPEUTICE
Prof. Univ. Dr. Ioana Berindan
UMF „Iuliu Hațieganu” Cluj Napoca

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Management logistic și Comunicare
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• Sâmbătă, 21 septembrie 101

18-21 septembrie 2019 3

Comitet Organizare Dr. Gheorghța Isvoranu

4 18-21 septembrie 2019

MIERCURI, 18 .09.2019: „Imunologia (tot) mai aproape de adevăr”

09.00–09.15 Deschiderea oﬁcială

09.15–09.45 Conferință plenară

09.45-10.00 Prezentarea Asociației Române a Pacienților cu Imunodeﬁciențe Primare

10.00–10.30 Conferință plenară

10.45-11.15 Conferință plenară

Pattern-ul imun în melanomul cutanat

11.15–12.30 Prezentări orale: Imunologie fundamentală

Modularea răspunsului imun în diabetul zaharat

6 18-21 septembrie 2019

Studiul in vitro al efectului indus de MnCl2

Interleukinele 1-41: Roluri pro- și antitumorale

13.30–14.00 Conferință plenară

14.00–15.30 Prezentări orale: Imunologie clinică

Expresia receptorilor „Checkpoint” B7 și a liganzilor lor în leucemia mieloidă acută

Proﬁlul citokinelor în parodontita marginală cronică

Proﬁlul citokinelor în pneumonia acută comunitară

Expresia ARN în boala parodontală

Interleukinele 19 și 33 în biologie și patologie

Populații și subpopulații de limfocite și celule dendritice în psoriazis

15.30-16.00 Conferință plenară

Inﬂamația și semnalizarea Wnt în osteoartrită

16.15–18.15 Sesiune plenară: „Vaccinuri”

Scopurile biologice ale vaccinării

Complexitatea dezvoltării vaccinurilor prin cercetare translațională: de la concept la evaluare

Caracterizarea prin spectrometrie de masă a antigenelor vaccinale - aplicare la fragmentarea

Optimizarea expresiei bacteriene a antigenelor din candidații de vaccin – aplicații la vaccinul

Evaluarea markerilor de diagnostic pentru infecția cu virusul rujeolos în contextul unei

Principale obiective în producerea de vaccinuri/adjuvanți și introducerea/menținerea lor pe

18.15–19.00 Prezentare postere

Efectele anti-tumorale ale unor compuși naturali în cancerul sferei ORL

Modiﬁcări morfopatologice induse de intoxicația acută cu MnCl2 pe model murin

Astro-imunologie: Proﬁlul de expresie genică în celule monocitare umane expuse la radiație

Markeri de celule stem corelați cu nivelul de factori angiogenici și citokine în glioame

Modularea răspunsului inﬂamator prin integrarea materialelor bioactive la nivelul pulpei

Evaluarea proliferării, citotoxicității și a efectelor apoptotice induse de nanoparticule

Leziunile musculare și strategie non-invazivă pentru regenerarea țesutului

O nouă metodă de extracție a antigenelor de melanom din specimene histopatologice ﬁxate

Importanța diagnosticului imunologic pentru pacienții cu toxocarioza și simptome alergice

Modele inﬂamatorii în evaluarea bolii renale cronice

Evaluarea biocompatibilității și a proprietăților regenerative ale biomaterialelor pe bază de

10 18-21 septembrie 2019

09.00–10.30 Workshop: „Imunologia transplantului – o continuă provocare”

Impactul potrivirii alelice HLA în supraviețuirea de lungă durată a pacienților cu transplant de

Dinamica monitorizării alogrefarii la pacienți cu transplant medular prin chimerism, dozarea

Aspecte ale imunologiei pediatrice în abordarea procedurii de transplant la copil

10.30–11.00 Conferință plenară

Characterization of Donor-Speciﬁc Alloreactive CD4+ and CD8+ Cellular Immune T Cell

18-21 septembrie 2019 11

11.15-11.45 Conferință plenară

Psoriazisul vulgar pediatric – what’s new?

11.45-13.15 Prezentări orale

Infecția HPV. Key messages

Prea frumos ca să ﬁe adevărat… și totuși…

Simpozion Cedraﬂon: „Bucuria ﬁecărui pas”

Durerea – Principii manageriale

Simpozion Detralex: „Atenție la neatenție”