Immunoradiometric Assay of Circulating C-Reactive Protein: Age-Related Values in the Adult General Population (Enzymes and Protein Markers‪)‬

Measurement of C-reactive protein (CRP), [5] the classical acute phase protein, is an extremely valuable marker of disease activity and response to therapy in a wide range of tissue-damaging, inflammatory, infective, and neoplastic conditions (1). The original automated nephelometric and turbidimetric immunoassays for CRP developed in the 1970s and the homogeneous enzyme and fluorescence polarization methods introduced in the early 1980s had limited sensitivity and poor precision in the low range. Thus, values below 5-10 mg/L could not be detected, although later improvements in some systems reduced the limit of detection to ~2 mg/L. This was not a problem because the median value for serum CRP in apparently healthy adults is ~0.8 mg/L, the 90th centile of the distribution in such subjects is ~3 mg/L, and all the information required for the classical applications of clinical CRP measurement in adults derives from increases in CRP concentration above these concentrations (1, 2). However, the recent use of more sensitive immunoassays for CRP has revealed exciting new information of both fundamental and clinical importance in three different areas: coronary heart disease and other complications of atherosclerosis (3-15), osteoarthritis (16), and neonatal infections (17). Although there now are several commercially available, routine clinical chemistry assays capable of precisely measuring circulating CRP concentrations within what was previously considered to be the reference interval, these were not available when we commenced our studies (3, 6). We therefore developed, and report here, a sensitive solid-phase monoclonal-polyclonal IRMA designed to measure CRP in plasma or serum of all subjects in the general population (12,18-21).