Its physiological role is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via C1q.
[8] Discovered by Tillett and Francis in 1930,[9] it was initially thought that CRP might be a pathogenic secretion since it was elevated in a variety of illnesses, including cancer.
[13] CRP was so named because it was first identified as a substance in the serum of patients with acute inflammation that reacted with the cell wall polysaccharide (C-polysaccharide) of pneumococcus.
This activates the complement system, promoting phagocytosis by macrophages, which clears necrotic and apoptotic cells and bacteria.
This so-called acute phase response occurs as a result of increasing concentrations of interleukin-6 (IL-6), which is produced by macrophages[6] as well as adipocytes[7] in response to a wide range of acute and chronic inflammatory conditions such as bacterial, viral, or fungal infections; rheumatic and other inflammatory diseases; malignancy; and tissue injury and necrosis.
[30] Therefore, the only factor that affects the blood CRP concentration is its production rate, which increases with inflammation, infection, trauma, necrosis, malignancy, and allergic reactions.
[citation needed] Other inflammatory mediators that can increase CRP are TGF beta 1, and tumor necrosis factor alpha.
ELISA and radial immunodiffusion methods are available for research use, while immunoturbidimetry is used clinically for CRP and nephelometry is typically used for hsCRP.
[37] CRP cut-off levels indicating bacterial from non-bacterial illness can vary due to co-morbidities such as malaria, HIV and malnutrition and the stage of disease presentation.
[39] CRP is a more sensitive and accurate reflection of the acute phase response than the ESR[40] (erythrocyte sedimentation rate).
[citation needed] Recent research suggests that patients with elevated basal levels of CRP are at an increased risk of diabetes,[41][42] hypertension and cardiovascular disease.
[52] In a meta-analysis of 20 studies involving 1,466 patients with coronary artery disease, CRP levels were found to be reduced after exercise interventions.
[56][57] Nevertheless, a level above 2.4 mg/L has been associated with a doubled risk of a coronary event compared to levels below 1 mg/L;[6] however, the study group in this case consisted of patients who had been diagnosed with unstable angina pectoris; whether elevated CRP has any predictive value of acute coronary events in the general population of all age ranges remains unclear.
Currently, C-reactive protein is not recommended as a cardiovascular disease screening test for average-risk adults without symptoms.
[citation needed] CRP levels also tend not to be elevated in systemic lupus erythematosus (SLE) unless serositis or synovitis is present.
Patients with high CRP concentrations are more likely to develop stroke, myocardial infarction, and severe peripheral vascular disease.
[40][61] High levels of CRP has been associated to point mutation Cys130Arg in the APOE gene, coding for apolipoprotein E, establishing a link between lipid values and inflammatory markers modulation.
[66] C-reactive protein (CRP), a marker of systemic inflammation, is also increased in obstructive sleep apnea (OSA).
[67] Patients with OSA have higher plasma CRP concentrations that increased corresponding to the severity of their apnea-hypopnea index score.
Rheumatoid arthritis associated antibodies together with 14-3-3η YWHAH have been reported to complement CRP in predicting clinical and radiographic outcomes in patients with recent onset inflammatory polyarthritis.
Mechanistically, CRP also appears to influence osteoclast activity leading to bone resorption and also stimulates RANKL expression in peripheral blood monocytes.