Hypogammaglobulinemia

Practice Essentials
Hypogammaglobulinemia refers to a set of
clinicolaboratory entities with varied causes and
manifestations. The common clinical feature of
hypogammaglobulinemia relates to a predisposition
toward infections that normally are defended
against by antibody responses (including
Streptococcus pneumoniae and Haemophilus
influenzae infections).

Essential update: Rituximab increases incidence of
hypogammaglobulinemia
In a retrospective study from Memorial Sloan-
Kettering Cancer Center, Casulo et al examined the
relation between rituximab and
hypogammaglobulinemia in 211 patients with B-
cell lymphoma who were treated with rituximab
and assessed with serial quantitative serum
immunoglobulin (SIgG) concentrations before and
after treatment.[1] Of the 211 patients, 179 (85%)
had normal SIgG values before rituximab therapy;
after rituximab therapy, 39% of these 179 patients
had hypogammaglobulinemia. The risk was greater
in patients who received maintenance rituximab.[1]

Signs and symptoms
Most patients with hypogammaglobulinemia
present with a history of recurrent infections. A
detailed clinical history should emphasize the
following:

Family history
Age of onset
Site of infections
Type of microorganisms
Blood product reactions
Recurrent infections
Gastrointestinal symptoms
Musculoskeletal symptoms
Autoimmune and collagen vascular diseases
Physical findings may include the following:

Growth retardation
Abnormalities of lymphoid tissue and organs (eg, a
paucity of tonsillar tissue, adenoids, and peripheral
lymph nodes)
Developmental abnormalities (eg, of skeleton or
chest wall)
Abnormalities of skin and mucous membranes (eg,
Hipogamaglobulinemie

Essentials practic
Hipogamaglobulinemie se refer la un set de
entiti clinicolaboratory cu cauze variate i
manifestri. Trstura comun clinice de
hipogamaglobulinemie se refer la o predispoziie
spre infecii care n mod normal sunt aprate
mpotriva de raspunsuri de anticorpi (inclusiv
Streptococcus pneumoniae i Haemophilus
influenzae infecii).

Eseniale actualizare: Rituximab creste incidenta de
hipogamaglobulinemie
ntr-un studiu retrospectiv de la Memorial Sloan-
Kettering Cancer Center, Casulo et al examinat
relaia dintre rituximab i hipogamaglobulinemie la
211 pacieni cu limfom cu celule B, care au fost
tratati cu rituximab i evaluate cu imunoglobuline
serice (Sigg) concentraiile cantitative seriale
nainte i dup tratament [1] Din cele 211 de
pacienti, 179 (85%) au avut valori normale Sigg
nainte de tratament cu rituximab, dup tratament
rituximab, 39% din aceste 179 de pacienti au avut
hipogamaglobulinemie.. Riscul a fost mai mare la
pacientii care au primit rituximab ntreinere. [1]

Semne si simptome
Cei mai multi pacienti cu hipogamaglobulinemie
prezint cu un istoric de infecii recurente. O istorie
detaliata clinica ar trebui s sublinieze urmtoarele:

Istorie de familie
Vrsta de debut
Site-ul de infecii
Tip de microorganisme
Reacii de produse din snge
Infectii recurente
Simptome gastro-intestinale
Simptome musculo-scheletice
Boli vasculare autoimune i colagen
Constatrile fizice pot include urmtoarele:

Retard de cretere
Anomalii ale tesutului limfoid i organe (de
exemplu, un mic de esut amigdalian, polipi, i
ganglionii limfatici periferice)
Anomalii de dezvoltare (de exemplu, de schelet sau
piept de perete)
Anomalii ale pielii i mucoaselor (de exemplu,
cicatrici, erupii cutanate, livedo reticularis sau)
scars, rash, or livedo reticularis)
Ear, nose, and throat abnormalities (eg, tympanic
membrane perforation, purulent nasal discharge,
cobblestone pattern of pharyngeal mucosa, and
nasal exudate)
Pulmonary abnormalities (eg, bronchiectasis and
lung fibrosis with rales, rhonchi, and wheezing)
Cardiovascular abnormalities (eg, a loud pulmonic
heart sound, right ventricular heave, and tricuspid
regurgitation murmur suggesting pulmonary
hypertension; jugular venous distention, tender
hepatomegaly, and lower-extremity edema
suggesting cor pulmonale)
Neurologic abnormalities (eg, paralytic
poliomyelitis or deep sensory loss with decreased
vibratory and position sense of limb segments)
See Clinical Presentation for more detail.

Diagnosis
Laboratory studies that may be helpful include the
following:

Serum immunoglobulin
Antibody response after immunization
Isohemagglutinins
Peripheral blood lymphocyte immunophenotyping
Evaluation of cellular immunity (cutaneous
delayed-type hypersensitivity)
Complete blood count
Renal studies
GI studies (eg, alpha1 -antitrypsin)
Imaging studies that may be useful include the
following:

Chest radiography
High-resolution computed tomography (HRCT)
and nuclear scanning
The following tests may be considered as
circumstances warrant:

Adenosine deaminase (ADA) levels and mutations
in purine nucleoside phosphorylase
Flow cytometry or Western blotting
Restriction fragment length polymorphism (RFLP)
The following biopsy procedures may also be
considered:

Lymph node biopsy (for rapidly enlarging lymph
nodes to rule out infection or malignancy)
Rectal biopsy (for common variable
immunodeficiency [CVID] and immunoglobulin A
Anomalii ureche, nas, si gatului (de exemplu,
perforarea timpanului membrana, secretii nazale
purulente, model piatra de mucoasei faringiene,
nazale i exudat)
Anomalii pulmonare (de exemplu, bronsiectazii i
fibroz pulmonar cu raluri, sforait, si respiratie
suieratoare)
Anomalii cardiovasculare (de exemplu, un sunet
puternic pulmonara inima, ventriculului drept
alunecare de teren, i suflu regurgitare tricuspidian
sugereaza hipertensiune pulmonara, distensia
venelor jugulare, hepatomegalie licitaie, i edem
extremitatea inferioara sugernd cord pulmonar)
Anomalii neurologice (de exemplu, poliomielita
paralitica sau pierderea senzorial profund cu
scderea sens vibratorie i poziia de segmente ale
membrelor)
A se vedea tabloul clinic pentru mai multe detalii.

Diagnostic
Studiile de laborator care pot fi utile includ
urmtoarele:

Imunoglobuline serice
Raspuns de anticorpi dup imunizare
Isohemagglutinins
Periferic limfocitelor imunofenotipare sange
Evaluarea a imunitii celulare (cutanate de
hipersensibilitate de tip ntrziat)
Hemograma completa
Studiile renale
Studiile GI (de exemplu, alfa1-antitripsina)
Studii de imagistica, care pot fi utile include
urmtoarele:

Radiografia toracica
Tomografie de inalta rezolutie computerizata
(HRCT) i scanarea nuclear
Urmatoarele teste pot fi considerate de mprejurri:

Dezaminazei (ADA), nivelurile si mutatii adenozin
in fosforilaza purinei nucleozidici
Citometrie n flux sau Western blot
Fragmentelor de restricie polimorfismului lungime
(RFLP)
Poate fi, de asemenea, luate n considerare
urmtoarele proceduri de biopsie:

Biopsie a ganglionilor limfatici (pentru extinderea
rapid a ganglionilor limfatici pentru a exclude
infectii sau tumori maligne)
[IgA] deficiency)
Thymus biopsy (indicated only for thymoma)
See Workup for more detail.

Management
Replacement therapy with immunoglobulin G
(IgG), administered intravenously (IVIG) or
subcutaneously (SCIG), is the treatment of choice
for most primary immunodeficiency syndromes,
including the following:

X-linked agammaglobulinemia (Bruton disease;
XLA)
CVID
Severe combined immunodeficiency (SCID)
Hyper-IgM
ADA deficiency
Wiskott-Aldrich syndrome (WAS)
Treatment of secondary hypogammaglobulinemia
is directed at the underlying cause, as follows:

IVIG is not indicated for lymphoproliferative
disorders unless immunoglobulin levels are low in
association with recurrent infections or if IVIG is
being used for autoimmune conditions that may
accompany these disorders
Live vaccines should not be given to patients with
T-cell disorders, XLA, or other severe B-cell
disorders or to the family members of such patients
High doses of IVIG or intrathecal immunoglobulin
may be beneficial in patients with XLA who have
enteroviral meningoencephalitis
Hematopoietic stem cell transplantation (HSCT) is
the treatment of choice for SCID and, if a matched
donor is available, for ADA deficiency[2]
Enzyme replacement with polyethylene glycol-
ADA (PEG-ADA) may be an effective alternative
for patients with ADA deficiency who lack an
HLA-identical sibling
Tumor necrosis factor (TNF) inhibitors have been
used to treat granulomatous diseases in patients
with CVID
Gene therapy has been shown to be successful in
reconstituting immune function in infants with X-
linked SCID, but efficacy is less proven in older
children and young adults[3]
See Treatment and Medication for more detail.

Background
Hypogammaglobulinemia refers to a set of
clinicolaboratory entities with varied causes and
Biopsie rectala (pentru variabila imunodeficientei
[CVID] i imunoglobulina A [IgA] deficit comun)
Biopsia timusului (indicat numai pentru timom)
Vezi Reacia conduce pentru mai multe detalii.

Administrare
Terapia de substituie cu imunoglobulina G (IgG),
administrat intravenos (IGIV) sau subcutanat
(SCIG), este tratamentul de alegere pentru cele mai
multe sindroame de imunodeficien primar,
inclusiv urmtoarele:

Agamaglobulinemie X-legat (boala Bruton; XLA)
CVID
Imunodeficiene combinate severe (SCID)
Hyper-IgM
Deficit de ADA
Sindromul Wiskott-Aldrich (WAS)
Tratamentul hipogamaglobulinemie secundar este
ndreptat la cauza de baza, dupa cum urmeaza:

IGIV nu este indicat pentru tulburri
limfoproliferative excepia cazului n care
nivelurile de imunoglobuline sunt sczute n
asociere cu infectii recurente sau dac IGIV este
folosit pentru boli autoimune, care pot nsoi aceste
tulburari
Vaccinurile vii nu trebuie administrate la pacienii
cu tulburri T-mobile, XLA, sau alte tulburri de
celule B grave sau a membrilor de familie ai unor
astfel de pacieni
Doze mari de IGIV sau de imunoglobuline
intratecal poate fi benefica la pacientii cu XLA care
au meningoencefalita enteroviral
Transplant de celule stem hematopoietice (HSCT)
este tratamentul de alegere pentru SCID i, n cazul
n care un donator potrivit este disponibil, de deficit
de ADA [2]
nlocuirea enzimei cu polietilen glicol-ADA (PEG-
ADA), poate fi o alternativa eficienta pentru
pacientii cu deficit de ADA, care nu dispun de un
frate HLA-identice
Factor (TNF), inhibitori de necroz tumoral au
fost folosite pentru a trata bolile granulomatoase la
pacientii cu CVID
Terapia genica sa dovedit a fi de succes n
reconstituirea sistemului imunitar la copii cu SCID
X-legate, dar eficacitatea este mai puin dovedit la
copiii mai mari si adultii tineri [3]
A se vedea, de tratament si medicatie pentru mai
multe detalii.
manifestations. Several codes in the International
Classification of Diseases, 9th edition (ICD-9)
relate to disorders in which
hypogammaglobulinemia is a primary feature.
These include deficiencies of humoral immunity,
which is coded 279.0. The common clinical feature
of hypogammaglobulinemia relates to a
predisposition toward infections that normally are
defended against by antibody responses. These
include Streptococcus pneumoniae and
Haemophilus influenzae infections, which
frequently involve the respiratory tract.

While primary immunodeficiencies causing
hypogammaglobulinemia are relatively uncommon,
the demand for gammaglobulin treatment has
grown and placed demands on the limited supply of
this treatment. Therefore, an awareness of the
appropriate diagnostic and therapeutic approaches
to hypogammaglobulinemia is important.

Specific immune responses are based on 2 major
components, ie, (1) humoral immunity, involving
antibodies produced by B lymphocytes also known
as B cells, and (2) cellular immunity, requiring
recognition by T lymphocytes or T cells.
Immunoglobulins (Igs) produced by B cells play a
central role in humoral immunity, and deficiency
may result in dramatic consequences for the body's
defense against infections. Disorders of the
immune system that can result in
hypogammaglobulinemia can involve B cells, T
cells, or both.

The information in this article is not meant to be a
comprehensive review but rather, a guide on the
differential diagnoses of hypogammaglobulinemia.
This article provides a review of the causes, clinical
symptoms, diagnosis, complications, and treatment
of the more common forms of
hypogammaglobulinemia.

Pathophysiology
Immunoglobulins play crucial roles in the immune
response by recognizing foreign antigens and
triggering effector mechanisms and physiologic
responses that attempt, and usually succeed, in
eliminating the invading organism bearing that
antigen. The human immune system is capable of
producing up to 109 different antibody species to
interact with a wide range of antigens. The known

Fundal
Hipogamaglobulinemie se refer la un set de
entiti clinicolaboratory cu cauze variate i
manifestri. Mai multe coduri din Clasificarea
Internaional a Maladiilor, ediia a 9-(ICD-9) se
refer la tulburri n care hipogamaglobulinemie
este o caracteristic principal. Acestea includ
deficiene de imunitatea umorala, care este codat
279.0. Trstura comun clinice de
hipogamaglobulinemie se refer la o predispoziie
spre infecii care n mod normal sunt aprate
mpotriva de raspunsuri de anticorpi. Acestea
includ Streptococcus pneumoniae i Haemophilus
influenzae infecii, care implic frecvent tractul
respirator.

n timp ce imunodeficiene primare cauzeaz
hipogamaglobulinemie sunt relativ rare, cererea de
tratament gamaglobulinelor a crescut i plasat
cererile pe oferta limitata de acest tratament. Prin
urmare, o contientizare a abordarilor de diagnostic
si terapeutice adecvate pentru
hipogamaglobulinemie este important.

Raspunsurile imune specifice se bazeaz pe dou
componente majore, respectiv, (1) umorale, care
implic anticorpii produsi de limfocitele B, de
asemenea, cunoscut ca celulele B, i (2) imunitatea
celulara, care necesit recunoaterea de limfocite T
sau celule T. Imunoglobuline (IGS), produs de
celulele B joaca un rol central in imunitatea
umorala, si deficienta poate duce la consecine
dramatice pentru aprare al organismului mpotriva
infeciilor. Tulburari ale sistemului imunitar, care
poate duce la hipogamaglobulinemie pot implica
celulele B, celulele T, sau ambele.

Informaiile din acest articol nu este menit s fie o
revizuire complet, ci, mai degrab, un ghid cu
privire la diagnosticul diferenial de
hipogamaglobulinemie. Acest articol ofer o
analiz a cauzelor, simptomelor clinice, diagnostic,
complicatii, tratament i dintre cele mai comune
forme de hipogamaglobulinemie.

Fiziopatologie
Imunoglobuline juca un rol crucial in raspunsul
imun prin recunoaterea antigenelor strine i
declaneaz mecanismele efectoare si raspunsurile
fiziologice care ncearc, i de obicei reuesc, n
immunoglobulin isotypes, named after their heavy-
chains, are IgG1, IgG2, IgG3, IgG4, IgM, IgA1,
IgA2, IgD, and IgE.

The structural diversity of Ig isotypes is reflected in
their functions. IgG isotypes represent the major
component (approximately 85%) of all antibodies
in serum, and IgA predominates in secretions. By
binding to receptors for their Fc regions, they
mediate many functions, including antibody-
dependent cell-mediated cytotoxicity,
phagocytosis, and clearance of immune complexes.
IgM plays a pivotal role in the primary immune
response. IgM, IgG1, IgG3, and, to a lesser degree,
IgG2, fix and activate complement by the classical
pathway. Most types of phagocytes bear receptors
for the Fc of IgG.

In general, IgG1 is the major component of the
response to protein antigens (eg, antitetanus and
antidiphtheria antibodies). IgG2 and some IgG3 are
produced in response to polysaccharide antigens
(eg, antipneumococcal antibodies). Some patients
who lack IgG2 still respond to polysaccharide
antigens. IgG3 seems to play an important role in
the response to respiratory viruses. IgA and, to a
lesser extent, IgM, produced locally and secreted
by mucous membranes, are the major determinants
of mucosal immunity. IgG is the only Ig class that
crosses the placenta. This occurs mostly during the
third trimester of pregnancy and provides the full-
term infant with effective humoral immunity during
the first months of life. The levels of maternal
antibodies slowly fall because of catabolism,
reaching nonprotective levels by about 6 months of
age. During this time, the infant begins endogenous
production of IgG.

With the advent of serum protein electrophoresis,
the globulins were considered to be comprised of 3
major fractions, alpha being the fastest moving and
gamma the slowest. The gamma-globulin fraction
is primarily composed of immunoglobulins, of
which IgG is the largest component, constituting
about 80% of the serum immunoglobulins in
normal plasma, and is distributed throughout the
entire volume of extracellular fluid.
Immunoglobulins are produced by plasma cells.

Catabolism of immunoglobulins occurs in a
concentration-dependent manner, with higher
eliminarea invadeze organismul poart ca antigen.
Sistemul imunitar uman este capabil de a produce
pn la 109 de specii diferite de anticorpi pentru a
interaciona cu o gam larg de antigene. Cele
isotypes imunoglobulin cunoscute, dup numele
lor grele lanuri, sunt IgG1, IgG2, IgG3, IgG4,
IgM, IgA1, IgA2, IgD, i IgE.

Diversitatea structural a Ig isotypes se reflect n
funciile lor. Isotypes IgG reprezint componenta
major (aproximativ 85%) din toate anticorpi n
ser, i IgA predomin n secreiile. Prin legarea de
receptorii pentru regiunile lor Fc, ei mediaz multe
funcii, inclusiv mediat celular dependent de
anticorpi citotoxicitate, fagocitoza, iar clearance
complexelor imune. IgM joaca un rol esential in
raspunsul imun primar. IgM, IgG1, IgG3, i, ntr-o
msur mai mic, IgG2, repara i de a activa
complementul pe calea clasic. Cele mai multe
tipuri de fagocite poart receptori pentru Fc al IgG.

n general, IgG1 este componenta major a
rspunsului la antigene proteine (de exemplu,
antitetanus i anticorpii antidiphtheria). IgG2 i
unele IgG3 sunt produse ca rspuns la antigenele
polizaharidice (de exemplu, anticorpi
antipneumococcal). Unii pacieni care nu dispun de
IgG2 mai rspunde la antigeni polizaharide. IgG3
pare s joace un rol important n rspunsul la
virusurile respiratorii. IgA i, n mai mic msur,
IgM, produse la nivel local i secretat de
membranele mucoase, sunt principalii factori
determinani ai imunitatea mucoaselor. IgG este
singura clasa de Ig care traverseaza placenta. Acest
lucru se ntmpl mai ales n al treilea trimestru de
sarcin i ofer copilul la termen cu imunitate
umoral eficace n primele luni de viata. Nivelurile
de anticorpi materni cad ncet din cauza catabolism,
atingnd niveluri nonprotective de aproximativ 6
luni. n acest timp, copilul ncepe producia
endogen de IgG.

Odat cu apariia de electroforeza proteinelor
serice, de globuline au fost considerate a fi compus
din 3 fraciuni majore, Alpha fiind cel mai rapid n
micare i gamma cel mai lent. Fraciunea gamma-
globulina este compus n principal din
imunoglobuline, din care IgG este cea mai mare
component, constituind circa 80% din
imunoglobulinelor serice din plasma normal, i
este distribuit n ntregul volum de lichid
concentrations being cleared faster. This
phenomenon may have therapeutic implications: a
specific, saturable Fc receptor (termed FcRn, which
differs from phagocyte Fc receptors) is thought to
promote cellular recycling of intact
immunoglobulin molecules, preventing their
catabolism by lysosomes and therefore prolonging
their half-life in the circulation. Normal IgG
molecules have a half-life of 21-28 days. Renal
clearance occurs for immunoglobulin fragments,
not intact molecules. These fragments may be
elevated in certain disease states and may be
detected, for example, as myeloma -associated
Bence Jones proteins in the urine.

Acquired or secondary hypogammaglobulinemia
usually involves a few general categories. The
major types include medications, renal loss of
immunoglobulins, gastrointestinal immunoglobulin
loss, B-cellrelated malignancies, and severe burns.
Renal loss of immunoglobulins is exemplified by
nephrotic syndrome, in which IgG loss is usually
accompanied by albumin loss. Gastrointestinal loss
occurs in protein-losing enteropathies and intestinal
lymphangiectasia. Increased catabolism occurs in
various diseases, including the B-cell lineage
malignancies and severe burns but also in
dystrophic myotonia.

Hypogammaglobulinemia may result from lack of
production, excessive loss of immunoglobulins, or
both. Congenital disorders affecting B-cell
development can result in complete or partial
absence of one or more Ig isotypes. The classic
form of this type of disorder is Bruton
agammaglobulinemia, also known as X-linked
agammaglobulinemia (XLA). Because B, T, and
natural killer (NK) cells share a common
progenitor, defects occurring at early
developmental stages may result in combined
immunodeficiency involving all cell types,
although defects further down the differentiation
pathways may result in deficiencies of a single cell
type only.

The symptoms depend on the type and severity of
the Ig deficiency and the presence or deficiency of
cellular immunity. In general,
hypogammaglobulinemia results in recurrent
infections with a restricted set of microorganisms
primarily localized to the upper and lower airways,
extracelular. Imunoglobulinele sunt produse de
celulele plasmatice.

Catabolismul imunoglobulinelor se produce ntr-un
mod dependent de concentraie, la concentraii mai
mari fiind resping repede. Acest fenomen ar putea
avea implicatii terapeutice: un receptor specific,
saturabil Fc (numit FcRn, care difer de la
receptorii fagocite Fc) este gandit pentru a promova
reciclarea celular de molecule de imunoglobuline
intacte, prevenind catabolismul lor de lizozomi i,
prin urmare, prelungirea lor de njumtire n
circulaie . Molecule normale de IgG au un timp de
njumtire de 21-28 de zile. Eliminarea renal are
loc de fragmente de imunoglobuline, nu molecule
intacte. Aceste fragmente pot fi crescute n anumite
stri de boal i pot fi detectate, de exemplu, ca
mielom-asociate proteine Bence Jones n urin.

Dobndite sau hipogamaglobulinemie secundar
implic, de obicei, cteva categorii generale. Cele
mai importante tipuri includ medicamente,
pierderea renal de imunoglobuline,
imunoglobuline pierderi gastro-intestinale,
afectiuni maligne B-celule legate, i arsuri grave.
Pierderea renal de imunoglobuline este
exemplificat de sindrom nefrotic, n care pierderea
IgG este de obicei nsoit de pierderea albumin.
Pierderea gastro-intestinale la enteropatii proteine-a
pierdut i intestinale limfangiectazaii. Catabolism
crescut apare n diferite boli, inclusiv boli maligne
filiatie de celule B i arsuri grave, dar, de
asemenea, n myotonia distrofice.

Hipogamaglobulinemie pot rezulta din lipsa de
producie, pierderi excesive de imunoglobuline, sau
ambele. Tulburri congenitale care afecteaz
dezvoltarea celulelor B poate duce la absena
complet sau parial a uneia sau mai multor
izotipuri Ig. Forma clasic a acestui tip de tulburare
este Bruton agamaglobulinemie, de asemenea,
cunoscut sub numele de agamaglobulinemie X-
legat (XLA). Deoarece B, T, si natural killer (NK)
celule progenitoare au o comun, defecte care apar
n fazele incipiente de dezvoltare poate duce la
imunodeficientei combinate implic toate tipurile
de celule, cu toate defectele mai jos de cai de
diferentiere poate duce la deficiente de un singur
tip de celule numai .

Simptomele depind de tipul i severitatea
although bacteremia and GI infections can also
occur. Patients with associated defects in cellular
immunity usually present with opportunistic viral,
fungal, or parasitic infections.

For a detailed discussion of inherited causes of
hypogammaglobulinemia, see Pure B-Cell
Disorders.

Epidemiology
Frequency
The incidence of genetically determined
immunodeficiency is relatively low when
compared with acquired immunodeficiency.
Humoral immunity deficiencies represent 50% of
all primary immunodeficiencies. IgA deficiency is
the most common antibody deficiency syndrome,
followed by common variable immunodeficiency
(CVID). The incidence of these 2 disorders is
estimated to be 1 case in 700 persons and 1 case in
5,000-10,000 persons of European ancestry,
respectively. Selective IgM deficiency is a rare
disorder. IgG4 deficiency is very common and is
detected in 10-15% of the general population. It
usually does not cause clinical
hypogammaglobulinemia and usually is
asymptomatic.

Mortality/Morbidity
Patients with hypogammaglobulinemia experience
an increased incidence of a large spectrum of
infections starting at an early age.

In conditions in which B-cells are present, such as
CVID, the risk of autoimmune disorders and cancer
is increased, adding to the morbidity and mortality
due to infection.[4, 5] Recurrent infections may
ultimately lead to significant end-organ damage,
particularly involving the respiratory system.
Malignancies remain a major cause of death.
Patients with certain inherited disorders may not
survive infancy or early childhood, and growth may
be affected for those who survive. Patients with
severe combined immunodeficiency (SCID) die
before the second year of life if they do not receive
allogeneic stem cell (bone marrow or cord blood)
transplantation,[2] while most patients with
reticular dysgenesis die in early infancy. Of
patients with X-linked agammaglobulinemia
(XLA), 15% die of infectious complications by age
20 years, but many have relatively normal life
deficitului de Ig i prezena sau deficit de imunitate
celular. n general, rezultate
hipogamaglobulinemie n infecii recurente cu un
set restrns de microorganisme localizate n
principal la cile respiratorii superioare i
inferioare, dei infeciile bacteriemie i GI pot
aprea, de asemenea. Pacientii cu defecte legate de
imunitatea celulara, de obicei, prezent cu infectii
virale, fungice sau parazitare oportuniste.

Pentru o discuie detaliat a cauzelor motenite de
hipogamaglobulinemie, vezi Pure Tulburari B-Cell.

Epidemiologie
Frecven
Incidena determinate genetic imunodeficienei este
relativ sczut n comparaie cu imunodeficienei
dobndite. Deficiene imunitii umorale reprezint
50% din toate imunodeficiene primare. Deficit de
IgA este cel mai frecvent sindrom deficit de
anticorpi, urmat de imunodeficien variabil
comun (CVID). Incidenta acestor 2 afectiuni este
estimat la 1 caz la 700 de persoane i 1 caz n
5,000-10,000 persoane de origine europeana,
respectiv. Deficit de IgM selectiv este o afectiune
rara. IgG4 deficit este foarte comun i este
detectat n 10-15% din populatia generala. Este de
obicei, nu produce hipogamaglobulinemie clinice i
de obicei este asimptomatic.

Mortalitatea / Morbiditatea
Pacientii cu hipogamaglobulinemie experimenta o
incidenta crescuta a unui spectru larg de infectii
ncepnd de la o vrst fraged.

n condiiile n care B-celule sunt prezente, cum ar
fi CVID, riscul de boli autoimune si cancer este
crescut, adugnd la morbiditate si mortalitate din
cauza infeciei. [4, 5] Infectiile recurente pot duce
n cele din urm la o deteriorare semnificativ
sfrit de organe , implicnd n special sistemul
respirator. Maligne ramane o cauza majora de
deces.
Pacienilor cu anumite afeciuni motenite nu pot
supravieui copilarie sau copilaria timpurie, iar
creterea poate fi afectat pentru cei care
supravietuiesc. Pacientii cu severa imunodeficientei
mor combinate (SCID), nainte de al doilea an de
via n cazul n care nu primesc alogen de celule
stem (maduva osoasa sau sangele din cordonul
ombilical) transplant, [2] n timp ce majoritatea
spans if they are diagnosed and begin
immunoglobulin replacement therapy in early
childhood, before chronic lung infection begins.
Most patients with Wiskott-Aldrich syndrome
(WAS) die by the second decade of life if they
don't undergo transplantation.
Although gene therapy, bone marrow
transplantation, and immunoglobulin replacement
with intravenous or subcutaneous immunoglobulin
have had a significant impact on the natural history
of these diseases, these therapies are costly and
often require highly advanced facilities.
Race
No racial or ethnic predilection is recognized.

Sex
In children, primary immunodeficiencies are more
common in boys than in girls (male-to-female ratio
of approximately 5:1). In adults, primary
immunodeficiencies are diagnosed almost equally
in both sexes (male-to-female ratio of
approximately 1:1.4).

XLA, X-linked hyper-IgM syndrome, X-linked
SCID, and WAS are X-linked disorders for which
females are carriers and only males are affected.
However, WAS may occur if skewed inactivation
of the X chromosome occurs, resulting in an active
X chromosome carrying the Wiskott-Aldrich
mutation.
CVID and IgA deficiency affect both sexes equally.
They may be familial and frequently are associated
with autoimmune disorders.
Age
Symptoms in XLA typically begin around 6
months of age, when the concentrations of maternal
antibodies decline. However, this may vary
considerably, depending in large part on the baby's
exposure to other children carrying infectious
organisms. Unfortunately, the diagnosis is often
missed or delayed until significant morbidity has
occurred.[6] Some patients with atypical XLA
mutations and others with autosomal
hypogammaglobulinemia do not develop recurrent
infections and laboratory abnormalities until
adulthood and may be misdiagnosed with CVID or
selective antibody deficiency.
Infections in SCID, including severe candidiasis,
usually begin in the first months of life.
The symptoms of hyper-IgM syndromes usually
begin during the first 2 years of life. Chronic
pacientilor cu mor dysgenesis reticular in copilarie
timpurie. Dintre pacientii cu agamaglobulinemie X-
linked (XLA), 15% mor de complicatii infectioase
de varsta de 20 de ani, dar muli au via relativ
normal se ntinde n cazul n care sunt
diagnosticate si sa inceapa terapia de substitutie
imunoglobuline in copilaria timpurie, nainte de a
ncepe infectii pulmonare cronice. Cei mai multi
pacienti cu sindrom Wiskott-Aldrich (WAS), mor
de-al doilea deceniu al vieii, dac acestea nu fac
obiectul transplant.
Dei terapia genetica, transplantul de maduva
osoasa, si inlocuirea imunoglobuline cu
imunoglobuline intravenos sau subcutanat au avut
un impact semnificativ asupra istoriei naturale a
acestor boli, aceste terapii sunt costisitoare i
necesit de multe ori faciliti foarte avansate.
Ras
Nici o predilectie rasiala sau etnica este recunoscut.

Sex
La copii, imunodeficiene primare sunt mai
frecvente la baieti decat la fete (raportul brbai-de-
femeie de aproximativ 5:1). La adulti,
imunodeficiene primare sunt diagnosticate aproape
n mod egal la ambele sexe (raportul brbai-de-
femeie de aproximativ 1:1.4).

XLA, X-legat sindromul hiper-IgM, SCID X-
legate, i a fost sunt tulburri X-linked pentru care
femeile sunt operatorii de transport i doar brbaii
sunt afectate. Cu toate acestea, a fost poate aprea
dac inactivarea oblic a cromozomului X are loc,
rezultnd ntr-un cromozom X activ care transporta
mutatie Wiskott-Aldrich.
CVID si deficit de IgA afecteaza ambele sexe in
mod egal. Ele pot fi familial i frecvent sunt
asociate cu boli autoimune.
Vrst
Simptomele n XLA ncepe de obicei n jurul
vrstei de 6 luni, atunci cnd concentraiile de
anticorpi materne declin. Cu toate acestea, acest
lucru poate varia considerabil, n funcie n mare
parte de expunerea copilului la ali copii care
transport organisme infectioase. Din pcate,
diagnosticul este adesea pierdute sau ntrziate
pn cnd a avut loc o morbiditate semnificativa.
[6] Unii pacienti cu mutatii XLA atipice i altele cu
hipogamaglobulinemie autosomal nu dezvolte
infectii recurente i anomalii de laborator pn la
vrsta adult i poate fi gresit diagnosticata cu
cryptosporidia infection may be particularly
problematic in X-linked hyper-IgM, and stem cell
transplantation is best performed before this begins.
Patients with WAS start experiencing recurrent
bacterial infections during the first year of life. The
incidence of opportunistic infections, such as
Pneumocystis carinii, increases with time as
patients survive childhood.
Patients with reticular dysgenesis begin
experiencing recurrent infections soon after birth.
This ultimately leads to death in early infancy.
The age of onset of adenosine deaminase (ADA)
deficiency is variable. Most patients are diagnosed
during infancy. Because the failure of the immune
system is gradual, some cases are not diagnosed
until later childhood.
IgA deficiency may be asymptomatic in childhood,
and patients are usually diagnosed in early
adulthood.
CVID has a variable age of onset, usually occurring
by the third decade of life. However, on average,
CVID patients experience increased infections and
other symptoms for 10 years before their diagnosis
is recognized.
Ig deficiency with thymoma (Good syndrome)
affects adults aged 40-70 years.
deficit de anticorpi CVID sau selectiv.
Infecii la SCID, inclusiv candidoza severa, de
obicei, ncepe n primele luni de via.
Simptomele de sindrom de hiper-IgM, de obicei,
ncepe n primii 2 ani de via. Infectie cronica
cryptosporidium poate fi deosebit de problematic n
X-legate de hiper-IgM, si transplantul cu celule
stem este cel mai bine realizat nainte de aceasta
incepe.
Pacientii cu FOST ncepe confrunt cu infecii
bacteriene recurente in timpul primului an de via.
Incidena infeciilor oportuniste, cum ar fi
Pneumocystis carinii, crete cu timpul ca pacienti
supravietuiesc copilariei.
Pacientii cu dysgenesis reticular ncepe s se
confrunt infecii recurente la scurt timp dupa
nastere. Acest lucru n cele din urm duce la deces
in copilarie timpurie.
Varsta de debut a adenozindezaminazei (ADA)
deficit este variabil. Cei mai multi pacienti sunt
diagnosticati in timpul copilariei. Pentru c eecul
sistemului imunitar este treptat, unele cazuri nu
sunt diagnosticate pn copilrie mai trziu.
Deficit de IgA poate fi asimptomatica, in copilarie,
iar pacientii sunt de obicei diagnosticat la varsta
adulta precoce.
CVID are o vrst variabil de debut, de obicei, apar
de-al treilea deceniu de via. Cu toate acestea, n
medie, pacienti CVID experienta infectii a crescut
i alte simptome de 10 ani inainte de diagnostic lor
este recunoscut.
Deficit de Ig cu timom (sindromul Good) afecteaza
adultii in varsta de 40-70 de ani.