C

REACTIVE
PROTEIN

BY: M S RAHMAN
MODERATOR: DR. VARSHA A SINGH

Introduction

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CRP

An acute phase protein

In response to different inflammatory stimuli

Infection or tissue damage

Produced, mainly in the liver

Extra hepatic - neurons, atherosclerotic plaques,

monocytes, and lymphocytes.(The mechanisms
regulating synthesis - unknown)

Phylogenetically high- plasma protein

Acute-phase protein

Plasma concentration- increases (positive )

- decreases (negative)
- least 25 percent
- inflammatory
disorders.

Positive APP: - CRP,mannose binding protein,

Complement factors,ferritin,
Ceruloplasmin, serum
amyloid A etc.

Negative APP:- Albumin, transferrin, retinol-binding

protein, antithrombin,
transcortin

History

First acute-phase protein

It was discovered by Tillett and Francis in

1930 in the plasma of patients during
the acute phase of pneumococcal
infection.

CRP, named for its capacity to precipitate

the somatic C-polysaccharide of
Streptococcus pneumoniae.

STRUCTURE OF CRP

An annular (ring-shaped),pentameric
protein.

composed of five identical

nonglycosylated polypeptide subunits.

Half-life - 19 hours , constant , health

and disease.

Molecular weight -25106 Da

STRUCTURE OF CRP
Belongs to the pentraxin family of calcium dependent ligandbinding plasma proteins

Production

This is the early and rapid host response to

tissue injury.
Local expansion of pathogen number

Direct activation of compliment in tissues

Degranulation of mast cells

Release of inflammatory mediators

Systemically active mediators:

(IL-1, IL-6, TNF-)
Initiate production of CRP in liver

Activation of C/EBP gene at

Release of CRP in circulation

transcription level

Binding of CRP with phosphocholine

Receptors

Bacterial
cellwall

Apoptotic
Cell

Inflammated
tissue

Phagocytosis of bacteria with the production

of CRP

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CRP PRODUCTION AND KILLING OF

APOPTOTIC CELLS

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CRP PRODUCTION AND KILLING OF

INFLAMMATED TISSUE

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CLINICAL APPLICATION

Hepatic synthesis
Very

rapid, single stimulus.

Healthy young adultMedian

mg/l.

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Serum concentrations rise -

concentration 3.0

6 hr (above 5 mg/l )

-peaks around 48 hours.

RANGE OF CRP LEVELS

VIRAL INFECTIONS: <40mg/l

BACTERIAL INFECTIONS: 40-200 mg/l

SEVERE BACTERIAL INFECTIONS/ TRAUMA/

BURNS: >200 mg/l

Following an acute-phase stimulus-Increase up to 10000-fold

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Acute Inflammation

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A. Acute
inflammation:

Bacterial infection
Pneumococcal pneumonia

Acute rheumatic fever

Bacterial endocarditis

Staphylococcal osteomyelitis

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B. Chronic inflammation:

Systemic lupus erythematosis

Rheumatic arthritis
Reiters syndrome, psoriatic
arthriopathy, arthritis following jejunoileal bypass
Polyarteritis nodosa, disseminated
systemic vasculitis, coetaneous
vasculitis
Polymyalgia rheumatica

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Crohns disease

Ulcerative colitis

Dermomyositis

Osteoarthritis

Neoplastic diseases

Smokers

Obesity

Diabetes

C. Tissue injury:

Tissue injury and surgery

Acute myocardial ischemia

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CLINICAL USES OF CRP

Diagnostic

Prognostic

1. Screening

Infection

Inflammation/ Tissue
damage

Obesity/Hypertensionrisk of CHD

DM type II

Atherosclerosis.

2.Diagnosis of
MeningitisBacterial/ viral

Monitoring of the
response to treatment
of inflammation and
infection.

e.g. : acute pancreatitis

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Lab
Diagnosis
Quantitative

Semiquantitat
ive rapid latex
Agglutination

ELISA
Chemiluminescent
Immunoassay
Laser nephlometry
BNA nephelometer
Quantum dots and
immunochromatogr
aphic test
Immunoturbidimetr
y

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Qualitative

Latex
Agglutination

Latex agglutination test

Principle
CRP antigen + mono specific anti-human CRP
Agglutination

Detect greater then 6/ml CRP.

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Semiquantitave
Rapid latex slide test

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Quantitative Method
ELISA
Sandwich Assay

(Peroxidase)

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Quantum dots and immunochromatographic test

Quantum dots (QDs) are introduced as fluorescent probes
and immunochromatographic strips to develop
quantitative fluorescence point-of-care tests (QF-POCT) to
analyze C-reactive protein (CRP) levels

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Rabbit IgG

Human CRP
QD/anti-CRP
conjugate

sample pad

QD-labeled
goatanti-rabbit
Ab

Test line Control line Absorbent pad

CRP Ab2

Fluorescence intensity

Quantum dots and

immunochromatographic test

Distance from sample pad

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Quantitative Method
Chemiluminescent Immunoassay Kits

Use Streptavidin-HRP as
enzyme and enhanced
ECL system as substrate
reagent.

Relative luminosity values

(RLU) is scanned by
photon counter reader

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Quantitative Method
Laser Nephlometry

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Principle

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Light Source: polychromatic tungsten filament
lamp

Monochromator : captures light of multiple

wavelength and changes
to singlewavelength.
(

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Sample: Ag-Ab Complex
interaction of the incident light and
the sample volume

scattered light produced

Photodetector
an electronic signal
converted to a turbidity value.

Immunoturbidimetry-

Ab complex

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Light Source: polychromatic tungsten filament
lamp

Monochromator : captures light of multiple

wavelength and changes
to singlewavelength.
(

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Sample: Ag-Ab Complex
interaction of the incident light and
the sample volume

Absorbed light produced

Photodetector
an electronic signal
converted to a turbidity value.

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