Proteina C-reattiva / C-reactive protein

Segnalato dal Dott. Giuseppe Cotellessa  / Reported by Dr. Joseph Cotellessa

La PCR fa parte delle proteine di fase acuta, più specificamente delle proteine positive di fase acuta, cioè di quelle proteine che vedono i propri livelli sierici aumentare in risposta a uno stimolo infiammatorio. L'innalzamento della PCR è conseguenza dell'aumento di un'altra proteina detta interleuchina 6 (IL-6), prodotta principalmente dai macrofagi.

La PCR opsonizzando (cioè rivestendo la superficie di) microbi (in particolare alla Fosforilcolina) e cellule morte o irreparabilmente danneggiate, funge da complesso di attacco per le proteine del complemento, e inoltre stimola la fagocitosi mediata dai macrofagi. La PCR è quindi parte integrante dell'immunità di tipo innato, costituendo una delle molecole sentinella che più precocemente permettono di aggredire elementi esterni potenzialmente ostili.

I suoi livelli possono anche aumentare di 50.000 volte durante la risposta acuta, con un picco a 48 h dall'inizio dell'infiammazione.

La sua emivita è costante e i suoi livelli sierici sono correlati al tasso di produzione.

Test cardiologici

Danni alle pareti vasali possono essere causati dall'infiltrazione nella parete di cellule ed elementi infiammatori, per questo motivo i livelli di PCR possono essere utilizzati per stabilire il livello di rischio di patologie cardiovascolari. Si è notato come i livelli di PCR siano un marker di rischio indipendente dai livelli di colesterolo e trigliceridi presenti nel sangue. A prescindere dalle cause che hanno determinato l'innalzamento della concentrazione della proteina livelli di 2,4 mg/L si associano a un rischio doppio di insorgenza di patologia coronarica e infarto rispetto a soggetti con valori inferiori a 1 mg/L.

ENGLISH

CRP binds to the phosphocholine expressed on the surface of dead or dying cells and some bacteria. This activates thecomplement system, promoting phagocytosis by macrophages, which clears necrotic and apoptotic cells and bacteria.

This acute phase response occurs as a result of a rise in the concentration of IL-6, which is produced by macrophages as well as adipocytes  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. These conditions cause release of interleukin-6 and other cytokines that trigger the synthesis of CRP and fibrinogen by the liver.

CRP binds to phosphocholine on micro-organisms. It is thought to assist in complement binding to foreign and damaged cells and enhances phagocytosis by macrophages (opsonin-mediated phagocytosis), which express a receptor for CRP. It plays a role in innate immunity as an early defense system against infections.

CRP rises within two hours of the onset of inflammation, up to a 50,000-fold, and peaks at 48 hours. Its half-life of 18 hours is constant, and therefore its level is determined by the rate of production and hence the severity of the precipitating cause. CRP is thus a marker for inflammation that can be used to screen for inflammation.

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 CRP that were 73% higher than those in the lowest quartile. Although one group of researchers indicated that CRP may be only 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 been demonstrated in animal models only.

It has been hypothesized that patients with high CRP levels might benefit from use of statins. This is based on the JUPITER trial that found that elevated CRP levels without hyperlipidemia benefited. Statins were selected because they have been proven to reduce levels of CRP. Studies comparing effect of various statins in hs-CRP revealed similar effects of different statins. A subsequent trial however failed to find that CRP was useful for determining statin benefit.

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. Among those studies, higher CRP concentrations or poorer lipid profiles before beginning exercise were associated with greater reductions in CRP.

To clarify whether CRP is a bystander or active participant in atherogenesis, a 2008 study compared people with various genetic CRP variants. Those with a high CRP due to genetic variation had no increased risk of cardiovascular disease compared to those with a normal or low CRP. A study published in 2011 shows that CRP is associated with lipid responses to low-fat and high-polyunsaturated fat diets.

Fibrosis and inflammation

Scleroderma, polymyositis, and dermatomyositis elicit little or no CRP response. CRP levels also tend not to be elevated in SLE unless serositis or synovitis is present. Elevations of CRP in the absence of clinically significant inflammation can occur in renal failure. CRP level is an independent risk factor for atherosclerotic disease. Patients with high CRP concentrations are more likely to develop stroke, myocardial infarction, and severe peripheral vascular disease. Elevated level of CRP can also be observed in inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis.

High levels of CRP has been associated to point mutation Cys130Arg in APOE gene, coding for apolipoprotein E, establishing a link between lipid values and inflammatory markers modulation.

Obstructive sleep apnea

C-reactive protein (CRP), a marker of systemic inflammation, is also increased in obstructive sleep apnea (OSA). CRP and interleukin-6 (IL-6) levels were significantly higher in patients with OSA compared to obese control subjects. Patients with OSA have higher plasma CRP concentrations that increased corresponding to the severity of their apnea-hypopnea index score. Treatment of OSA with CPAP (continuous positive airway pressure) significantly alleviated the effect of OSA on CRP and IL-6 levels.

Coronary heart disease risk

Arterial damage results from white blood cell invasion and inflammation within the wall. CRP is a general marker for inflammation and infection, so it can be used as a very rough proxy for heart disease risk. Since many things can cause elevated CRP, this is not a very specific prognostic indicator. 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; 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.

Da:

https://it.wikipedia.org/wiki/Proteina_C-reattiva

https://en.wikipedia.org/wiki/C-reactive_protein