The value of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: do they imply new risk factors?

Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes chronic inflammation of the joints and several extra-articular manifestations that account for increased morbimortality of these patients. The involvement of B cells in RA pathophysiology was recognized early, with the discovery of rheumatoid factor antibody. Recently, a number of autoantibodies against citrullinated proteins have been described, of which anti-cyclic citrullinated peptide (anti-CCP) is the most specific for RA. A cohort of 937 patients with RA was studied to determine the clinical correlates of anti-CCP antibodies. The presence of anti-CCP antibodies correlated with worse joint involvement and several extra-articular manifestations, i.e., higher incidence of ischemic heart disease independent of classic cardiovascular factors and higher mortality rate. A multivariate logistic regression model showed that only anti-CCP antibodies were independently associated with the development of ischemic heart disease in patients with RA. The clinical value of anti-citrullinated protein antibodies and the relevance of anti-CCP antibodies in daily clinical practice are reviewed.