C Reactive Protein
Rajesh Purushothaman, Assoc Professor of Orthopaedics, Medical College, Calicut, India
- CRP is a protein secreted by liver into the circulation. It is named so because it was first identified by its ability to interact with capsular polypeptide of pneumococcus by Tillet and Francis in 1930. It is a 224 aminoacid protein. It has an annular pentameric disc shape. CRP gene is located on chromosome 1 (1q21-q23).
- Human beings have two types of immune system; Innate immune system and adaptive immune system. Innate immune system is inherited from invertebrates. It uses limited number of surface and intracellular germ line encoded proteins to recognise large groups of pathogens.
- The cells involved in innate immunity are the macrophages, natural killer cells and dendritic cells. They use pathogen associated molecular patterns(PAMPs) for identification of pathogens to trigger immune mechanisms. PAMPs are recognised by the pattern recognition receptors (PRR).
- Major PRR families include C-type lectins, leucine-rich proteins, macrophage scavenger receptor proteins, plasma pentraxins, lipid transferases and integrins. CRP is the first PRR to be identified. It belongs to the Pentraxin group of PRRs. Serum amyloid P is the other pentraxin PRR identified.
- Acute and chronic inflammatory conditions lead to secretion of interleukin-6 and other cytokines by macrophages and some adipocytes. Increased IL6 leads to secretion of CRP by liver.
- Its function is to bind to the phosphatidyl choline expressed on the surface of dead or dying cells and some bacteria and tag these cells (opsonisation), which help in the identification of that cell by the macrophages and leads to destruction of that cell by complement system or phagocytosis (opsonin mediated phagocytosis).
- During acute inflammation CRP level increases within 2 hours and peaks within 48 hours. It has a half life of 18 hours, and once the inflammation subsides level of CRP drops rapidly. Hence it helps to assess the response to treatment. CRP is elevated in a wide variety of conditions such as infections, inflammations, trauma, tissue necrosis, malignancies and autoimmune disorders.
- Scleroderma, polymyositis and dermatomyositis often leads to little or no elevation of CRP. CRP levels are normal in SLE, except when associated with synovitis or serositis.
- Recent publications have suggested increased risk of hypertension, diabetes and ischaemic heart disease in those with elevated basal levels of CRP. CRP levels more than 2.4mg/L is associated with twice the mortality when compared to those with levels less than 1mg/L. Statins have been shown to reduce CRP levels in those without hyperlipidemia(JUPITER study).
- Animal models have shown that blocking of CRP limits complement mediated cell necrosis in ischaemic injury.
- CRP is used a marker of inflammation. As it has a short half life, it’s level depends on the rate of production, hence the disease activity. CRP is measured in the serum by ELISA, immunoturbidometry, rapid immunodiffusion and visual agglutination. High sensitivity CRP (HS-CRP) measured using laser nephalometry measures low levels of CRP with increased sensitivity.
- Normal level of CRP is less than 10mg/L. Mild inflammations and viral infections lead to levels of 10-40mg/L, active inflammations and bacterial infections lead to levels of 40-200mg and severe bacterial infections lead to levels more than 200mg/L. Serial levels of CRP have been found to be a better predictor of response to treatment.