C Reactive Protein
It is thought to bind to phosphocholine, thus initiating recognition and phagocytosis of damaged cells.
Genetics and biochemistry
The CRP gene is located on the first chromosome (1q21-q23). CRP is a 224 residue protein with a monomer molar mass of 25106 Da.
Native CRP is a bit different as it has 10-subunits making two pentameric discs, with an overall molecular mass of 251060 Da.
Function
CRP is a member of the class of acute phase reactants as its levels rise dramatically during inflammatory processes occurring in the body. This increment is due to a rise in the plasma concentration of IL-6, which is produced predominantly by macrophages as well as adipocytes. CRP binds to phosphocholine on microbes.
It is thought to assist in complement binding to foreign and damaged cells and enhances phagocytosis by macrophages, which express a receptor for CRP. It is also believed to play an important role in innate immunity, as an early defense system against infections.
CRP rises up to 50,000 fold in acute inflammation, such as infection.
Its half-life is constant, and therefore its level is mainly determined by the rate of production (and hence the severity of the precipitating cause). Serum amyloid A is a related acute phase marker that responds rapidly in similar circumstances.
Diagnostic use
CRP is used mainly as a marker of inflammation.
Blood, usually collected in a serum-separating tube, is analysed in a medical laboratory or at the point of care.
Various analytical methods are available for CRP determination, such as ELISA, immunoturbidimetry, rapid immunodiffusion and visual agglutination.
Viral infections tend to give a lower CRP level than bacterial infection.
Normal reference ranges for blood tests are less than 5-6 mg/l.
Cardiology diagnostic test
Arterial damage is thought to result from inflammation due to chemical insults. CRP is a general marker for inflammation and infection, so it can be used as a very rough proxy for heart disease risk.
It retains its activity, but these losses open it up to glycosylation. The patterns are different across diseases, but similar amongst patients who had the same disease.
A 2003 study looked at patients with lupus, leukemia, tuberculosis, leishmaniasis, Cushing's syndrome and bone cancer. (Healthy subjects did not have enough CRP to successfully characterize "normal" CRP.)
Previous work had shown that CRP increased the rate at which a particular parasite could invade blood cells.
The study showed that the different CRPs had very different potencies in this regard. Although this did not demonstrate whether this glycation of CRP was a 'good thing' or a 'bad thing', it offered circumstantial evidence that the differing glycation is part of CRPs mode-of-action.
Role in cardiovascular disease
Recent research suggests that patients with elevated basal levels of CRP are at an increased risk of diabetes, hypertension and cardiovascular disease.
A study of over 700 nurses showed that those in the highest quartile of trans fat consumption had blood levels of C-reactive protein that were 73% higher than those in the lowest quartile. Although one group of researchers indicated that CRP may only be a moderate risk factor for cardiovascular disease, this study (known as the Reykjavik Study) was found to have some problems for this type of analysis related to the characteristics of the population studied, and there was an extremely long follow-up time which may have attenuated the association between CRP and future outcomes. Others have shown that CRP can exacerbate ischemic necrosis in a complement-dependent fashion and that CRP inhibition can be a safe and effective therapy for myocardial and cerebral infarcts; so far, this has only been demonstrated in animal models.
To measure the CRP level, a "high-sensitivity" CRP or hs-CRP test needs to be performed and analyzed by a laboratory. This is an automated blood test designed for greater accuracy in measuring low levels of CRP, which allows the physician to assess cardiovascular risk.
If a result in the low-risk range is found ( < 1 mg/L), it does not need repeating. Higher levels need repeating, and clinical evaluation as necessary.
Role in cancer
The role of inflammation in cancer is not well known.