C reactive protein

There are very few tests which are simple to carry out, done in almost all centers, use full to narrow down the list of provisional diagnosis and also useful for predicting future outcomes. C-RP is one of them. this presentation is not only for laboratory personal but also for MBBS students. Dental students, clinical department post graduates as well as clinicians.

1. C- REACTIVE PROTEIN Dr. Manan Shah

2. 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

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

4. CLASSIFICATION OF APP

5. PRODUCTION OF APP

6. PRODUCTION OF APP Levels will change approximately 1-2 hours after onset of a systemic inflammatory reaction or other stimuli

7. ACUTE PHASE REACTANT POSITIVE APPS C- Reactive protein (CRP) Serum Amyloid A (SAA) Ceruloplasmin α 2 Macroglobulin Fibrinogem Complement (C 3 /C 4 ) NEGATIVE APPS Albumin Transferin Transthyretin Retinol Binding Protein (RBP)

8. 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

9. 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

10. ACTIVATION OF CRP

11. 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

12. 3.Scavenging Action  CRP does not bind to normal cell membrane

13. 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

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

15. 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

16. 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

17. 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.

18. 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 .

19. 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

20. 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

21. 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

22. 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?

23. REFERENCES William MA, Snyder Lm. Wallach’s interpretation of diagnostic tests. 10 th 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. 1 st SA Ed. New delhi ; Elsevier;2015. McPherson RA, Pincus MR. HENRY’S Clinical Diagnosis and Management by Laboratory Methods. 22 rd Ed. China: Elsevier Saunders; 2011.

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