C-reactive protein

C-reactive protein, often abbreviated CRP, is an acute phase protein and a commonly measured laboratory parameter in the evaluation of inflammation. Its name comes from its ability to bind to the C-polysaccharide of pneumococci.

Biochemistry

CRP is a ring-shaped pentameric protein which binds to phosphocholine which is found on the cell membrane of dead cells and some bacteria. This binding activates the complement system. CRP also enhances phagocytosis of whatever CRP binds to, making it an opsonin.

CRP is synthesised in the liver.

CRP as a marker of infection or inflammation

The CRP is usually measured in the serum to evaluate acute inflammation. The reference range is <4-5 mg/L. It is also elevated after trauma or surgery, after other causes of necrosis such as myocardial infarction, and in some malignancies.

The half-life of CRP is 15-20 hours; as such, a reduction in acute inflammation is not reflected in the CRP level immediately. CRP peaks 36-50 hours after the onset of inflammation, but elevated levels of CRP can be measured after 8-12 hours after the insult.

The level of CRP correlates to some degree to the degree of inflammation and therefore the severity of the disease. An infection with CRP 200 is almost always more severe than one with 50.

The level of CRP can be used to distinguish between bacterial infection and other causes of inflammation, such as viral infections. There is no sharp cut-off, but markedly elevated levels > 100-150 is associated with bacterial infection. However, adenovirus infection can also cause a markedly elevated CRP.

Following CRP levels daily or over time can be used to monitor treatment response. If the CRP level decreases over time, one can conclude that the inflammation is decreasing and therefore that the treatment is efficacious.

CRP has a high negative predictive value for infection and inflammation, meaning that a negative result with high probability rules out severe infection and inflammation. A notable exception is some rheumatological disorders, for which erythrocyte sedimentation rate is a more sensitive marker of inflammation.

CRP as a marker of cardiovascular risk

Chronic inflammation increases the cardiovascular (CV) risk. CRP itself does not increase the risk, but it can be a marker of this risk-increasing inflammation. Newer laboratory methods allow more precise measurement of the CRP level, called high sensitivity CRP or micro CRP. This precision is unnecessary in case of evaluation for infection, but it can be useful in the determination of cardiovascular risk, as the inflammation in these otherwise healthy individuals is so low-grade that high sensitivity measurements are necessary to detect the small elevations in CRP. This chronic low-grade inflammation is sometimes called metabolic inflammation.

High sensitivity CRP (hsCRP) below 1 mg/L confers a lower CV risk, while a hsCRP > 3 confers a higher risk. In case of chronic low-grade inflammation, hsCRP levels of 3-10 are usually seen.

CRP as a marker of malignancy

CRP is elevated, usually only mildly (10-100 units) in some malignancies, most notably haematological ones.