Rapid Automated High Sensitivity Enzyme Immunoassay of C-Reactive Protein

Abstract

The concentration of C-reactive protein (CRP), the classic acute phase plasma protein, increases rapidly in response to most forms of tissue injury, infection, and inflammation (1)(2)(3). CRP is secreted only by hepatocytes, where its synthesis is regulated by cytokines, of which IL-6 is the most important. The t 1/2 of CRP in the circulation (∼19 h) is independent of the plasma concentration and is remarkably constant in all conditions (4). Thus, the only determinant of the plasma concentration is the rate of CRP production, which usually reflects closely the extent and activity of the current pathology. Furthermore, the CRP response is very sensitive, and although it is nonspecific and can never on its own be diagnostic, it provides an extremely useful objective marker in clinical practice, both in screening for organic disease and in monitoring disease activity and response to therapy (3). CRP concentrations in ostensibly healthy subjects have a very skewed distribution. In the first study with a sufficiently sensitive radioimmunoassay to detect CRP in all nondiseased sera tested, the median value was 0.58 mg/L (range, 0.068–8.2 mg/L) among 153 healthy blood donors (5). In our own original study of 468 volunteer blood donors, using the same 100% pure CRP as standard that was subsequently used to calibrate the World Health Organization International Standard for Human CRP (85/506) (6), the median value was 0.8 mg/L, and there was a tail of higher values, with the 90th percentile at 3 mg/L and the 99th percentile at 10 mg/L (7). In a more recent study based on the WHO standard and examining 143 apparently healthy blood donors, the median CRP value was 0.64 mg/L, and the 97.5th percentile was 3.11 mg/L (8). Routinely available immunochemical assay methods for plasma proteins have limited sensitivity, and until recently, …