C Reactive Protein (CRP)

Discovered in 1930, CRP is one of the acute phase proteins produced by the liver in response to tissue injury. CRP was recognized because of its ability to precipitate with C polysaccharide extract of Streptococcus pneumoniae. CRP is present in serum in nanogram quantities but can increase dramatically to hundreds of �g/ml within three days following tissue injury. Its level increases not only following infections but also due to trauma, burns, tissue necrosis etc. It is a protein of the pentraxin family and is related in structure to serum amyloid. It consists of five polypeptide subunits forming a molecule of total molecular weight 105 kD. C reactive protein is synthesized by hepatocytes and its production may be triggered by prostaglandin E1 or parogen. It binds to polysaccharides present in a wide range of bacterial, fungal and other cell walls or cell surfaces and to lecithin and to phosphoryl- or choline-containing molecules.

Since it reacted and precipitated the C polysaccharide of pneumococci it was initially thought to be an antibody due to the following reasons:

• Like antibody, CRP reacts with its substrate, cause lattice formations and precipitate.

• Like antibody, CRP can agglutinate RBCs that are coated with their substrates (passive hemagglutination).

• Like antibody, CRP can induce capsule swelling of pneumococci.

• Like antibody, CRP can induce complement activation.

• Like antibody, CRP acts as opsonin. CRP can opsonize RBC coated with C-polysaccharide for ingestion by phagocytes.

It was later found out that it is not an antibody because of following reasons:

• Its concentration rapidly decreased in sera of patients who had recovered from pneumococcal pneumonia. If it were antibody, it should have persisted for some considerable period of time.

• It was detected in sera of patients suffering from bacterial illness other than due to pneumococci.

• It was not detectable in sera from healthy individuals. However, now it is known that CRP is present in nanogram quantities in sera. 

• It does not have an immunoglobulin like structure.

Significance:
Being an acute phase protein it is primitive non-specific mechanism of innate immunity. CRP activates C1q to initiate the classical complement cascade in the absence of antibody. CRP binds microbial LPS phosphorylcholine and induces opsonization. 

Detection: 
It can be detected by passive latex agglutination test. The latex particles coated with C-polysaccharide are made to react with patient serum. Appearance of clumps is considered positive.