C- REACTIVE PROTEIN
Dr. Manan Shah

LEARNING OBJECTIVES
• Acute phase reactants/proteins
• What is APP
• Production of APP
• Example of APP
• C- Reactive protein
• Introduction
• Activation of CRP
• Normal functions of CRP
• Factors affecting
• Methods of detection
• Clinical importance
• High sensitivity CRP (hs-CRP)
• Summary
• References

ACUTE PHASE REACTANTS/PROTEINS
(APP)
• Definition:
 These are the class of proteins whose plasma
concentration increase or decrease in response
to inflammation

CLASSIFICATION OF APP
Positive
APPs
• Plasma
concentration
increases in
response to the
stimuli
Negative
APPs
• Plasma
concentration
Decreases in
response to the
stimuli

PRODUCTION OF APP

PRODUCTION OF APP
Acute Phase
Protein
Hepatic
Synthesis
Hepatocytes
Extrahepatic
synthesis
Epithelial Cells
Endothelial
cells
Connective
tissue. Eg.
Fibroblast
Adepocytes
Levels will change approximately 1-2
hours after onset of a systemic
inflammatory reaction or other stimuli

ACUTE PHASE REACTANT
POSITIVE APPS
• C- Reactive protein (CRP)
• Serum Amyloid A (SAA)
• Ceruloplasmin
• α2 Macroglobulin
• Fibrinogem
• Complement (C3/C4)
NEGATIVE APPS
• Albumin
• Transferin
• Transthyretin
• Retinol Binding Protein
(RBP)

C- REACTIVE PROTEIN
• Synthesize primarily in hepatocytes
• CRP Gene- Chromosome 1, Short arm
• Few cytokines especially, IL-6 and IL-1 regulate CRP at
transcritional level
• Normal range: Less than 10mg/L
• It has highest affinity for,
– Phosphocholine on bacteria
– Mixture of sphingomyeline and phosphatidylcholine in
eukaryotic membranes

C- REACTIVE PROTEIN
• CRP can recognize self ligands,
– Plasma lipoproteins
– Damaged cell membrane
– Several phospholopids
– Small nuclear ribonucleoprotein components
– Apoptotic Cells
• CRP Also bind to some extrinsic ligands,
– Phospholipid
– Capsular/cell body components of bacteria, fungi and
parasite and
– Plant particles

ACTIVATION OF CRP
Activates complement cascade
C1q attaches
CRP + Ligand

FUNCTIONS OF CRP
1. Anti Infective
 Opsonise particles for phagocytosis
 Activate Complement via classical pathway
2. Anti Inflammatory actions
 CRP helps in preventing systemic inflammation
 CRP aids in the release of neutrophils from blood
vessels, while preventing white cell adhesion to
vessel in non-inflamed tissue.
 Stimulate release of anti-inflammatory molecules from
monocytes

3.Scavenging Action
 CRP does not bind to normal cell membrane
Attracts neutrophils and monocytes to the site
Initiating an inflammatory reaction
Activates complement
Bind avidly to cells that are undergoing apoptosis or necrosis

FACTOR AFFECTING CRP LEVELS
Factor Effect
Gender women have higher levels
than men
Body mass effect Weight loss- Decrease
Ethnicity Blacks have higher levels
than whites
Exercise After exercise CRP levels
decrease
Alcohol consumption Decrease

METHOD FOR DETECTION OF CRP
• ELISA
• Immunoturbidimetry
• Rapid immunodiffusion and
• Visual Agglutination

CLINICAL IMPORTANCE OF CRP
• Elevated CRP levels:
– Osteoarthritis
– Predictive of coronary events (esp. in stable angina)
– Proinflammatory or prothrombotic effects
• Mild elevation of CRP levels:
– SLE
– Scleroderma
– Sjogren syndrome
– Dermatomyositis/Polymyositis

CLINICAL IMPORTANCE OF CRP
• Normalization of CRP levels:
– Helpful tool in determining the response to Antibiotic
therapy and duration of treatment
• Transplant cases,
– Elevated levels were seen in majority of kidney or heart
transplant
– Highly elevated in GVHD
– Changes in levels are not organ specific, like other
inflammatory conditions

CLINICAL IMPORTANCE OF CRP
• Cerebral vein or sinus thrombosis:
– An increase CRP is associated with a poorer short term
prognosis
• Giant cell arteritis:
– Thrombocytosis with platelet counts >400,000/μL and CRP
levels >2.45 mg/dL have been found to be to the strongest
laboratory predictors of a positive temporal artery biopsy.
• Pancreatitis:
– Level peaks 3 days after onset of pain
– At 48 hours, sensitivity = 65–100%, PPV = 37–77%.
– Level of 150 mg/L distinguishes mild from severe disease.

hs-CRP
• Definition:
– High sensitivity C-reactive protein (hs-CRP).
– Similar to CRP, it is also an Acute Phase Reactant.
– More sensitive than CRP especially for
cardiovascular injury.
– Normal range: less than 0.3mg/dL.

hs-CRP Uses
• Performing risk assessment for cardiovascular
diseases:
– Taken as an independent risk factor for CVD, Stroke
and Peripheral vascular disease.
– It also adds to the predictive value of total cholesterol
and HDL cholesterol for future events
• Determining risk of hypotension:
– hs-CRP has been reported as a risk factor for
hypotension

CARDIOVASCULAR RISK
CLASSIFICATION
• Cardiovascular disease risk assessment guidelines for
CRP recommended by the CDC and the American
heart association (CDC/AHA)
Risk Level CRP (mg/L)
Low <1.0
Intermediate 1.0-3.0
High >3.0

CARDIOVASCULAR RISK
CLASSIFICATION
• During the stroke,
• Failure of CRP to return to normal indicates tissue
damage in heart or elsewhere.
• Absence of a CRP increase raises the question of
necrosis in prior 2-10 days.
Serum Levels Duration
Start increasing Within 24-48 hours
Peaks 72 hours
Become negative After 7 days

SUMMERY
What is Acute Phase Protein?
Types of Acute Phase Protein & examples?
What does ‘C’ stand for in C-RP?
How C-Reactive Protein is useful & What is hs-
CRP?
Importance of hs-CRP in evaluation of CVD &
AMI?

REFERENCES
• William MA, Snyder Lm. Wallach’s interpretation of diagnostic tests.
10th Ed. New delhi: Wolters Kluver; 2015.
• Pearson TA, Mensah GA, Alexander RW, et al. Markers of
inflammation and cardiovascular disease. Application to clinical and
public health practice. A Statement for Healthcare Professionals
From the Centers for Disease Control and Prevention and the
American Heart Association. Circulation. 2003;107:499–511.
• Kumar, Abbas, Aster. Robbins & cotran Pathologic Basis of Disease.
1st SA Ed. New delhi; Elsevier;2015.
• McPherson RA, Pincus MR. HENRY’S Clinical Diagnosis and
Management by Laboratory Methods. 22rd Ed. China: Elsevier
Saunders; 2011.

 THANK YOU 