C-reactive protein in rheumatology: biology and genetics

Measurement of serum C-reactive protein (CRP) level is in widespread clinical use as a sensitive marker of inflammation. CRP has a role in the clearance of bacteria and of dying and altered cells, and might also have more complex immunomodulatory functions. Impaired clearance of apoptotic cells is important in the pathogenesis of systemic lupus erythematosus (SLE), raising the possibility that CRP dysregulation plays a part in this process. We review the available functional and genetic evidence supporting a role for CRP in the pathogenesis of SLE, but recognize that inconsistencies in the existing data mean that conclusions have to be interpreted with caution. More consistent is the evidence that the genetic variants influencing basal CRP level also influence the magnitude of the acute-phase rise in CRP level in active inflammation. Initial reports suggest that these genetic effects might be large enough to directly influence clinical decision-making processes that are based on an interpretation of CRP thresholds. This concept is explored further in this article, particularly in relation to the use of the CRP-based disease activity score in the evaluation of rheumatoid arthritis, where a systematic under-scoring or over-scoring of disease activity could result from a failure to consider the genetic influences on CRP level.