Reactive Protein

CRP, a pentraxin, is composed offive identical and noncovalently bonded subunits, each consisting of206 amino acid residues with a molecular mass of 23,017 kDa; thus, the total molecular mass of CRP is approx 118,000 kDa (10). The gene responsible for its synthesis is located on the proximal long arm of chromosome 1, at 7.7 kb, and is 2.5 kb long. The precise in vivo role of CRP is not totally clear; however, its properties are consistent with a fundamental role as a nonspecific defense mechanism. In response to tissue injury or infection, hepatocytes synthesize CRP after stimulation by cytokines, especially IL-6, IL-1 (3, and TNF-a (11). CRP binds to polysaccharides of many bacteria, fungi, and certain parasites in a calcium-dependent fashion, and once bound, it is a powerful activator of the classic complement system and can promote opsonization and phagocytosis offoreign substances. It is one of the most consistently increased and fastest-reacting acute-phase proteins (biological half-life of19 h), suggesting that it is part of the innate immune response (12). CRP concentrations may rise 1000-fold or more within 24-48 h oftissue injury. Mild inflammation and viral infections generally cause CRP concentrations to increase to approx 10-50 mg/L, and active inflammation and bacterial infections result in concentrations between 50 and 200 mg/L (13) (Fig. 1). Concentrations >200 mg/L are seen in more severe infections and in trauma.

Increases in CRP concentration, within the reference interval, are associated with future coronary events in apparently healthy men and women. These concentrations are below the detection limits ofthe traditional assays, because the median CRP values are about 1.5 mg/ L for both men and women. The AHA/CDC guidelines defined specific cut points for clinical interpretation: CRP concentrations <1 mg/L are considered low, 1-3 mg/L are average,

30 50

Fig. 2. Distribution of CRP concentration with age in healthy adults. (With permission from ref.26.)

and >3 mg/L indicate high relative risk, all of which are within the reference range of this protein (9).

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