Anti-citrulline antibodies in the diagnosis and prognosis of rheumatoid arthritis: evolving concepts

Citrulline is a non-standard amino acid that can be incorporated into proteins only by post-translational modification of arginine by peptidylarginine deiminase (PAD) enzymes during a variety of biologic processes, including inflammation. Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, with a prevalence of 0.3 to 1% worldwide, which leads to progressive joint erosion and substantial disability if not treated early. A reliable and specific test for a marker present early in the disease would be useful to identify RA patients prior to the occurrence of joint damage. A new group of autoantibodies, the anti-cyclic citrullinated peptide antibodies (anti-CCP), can be detected in up to 80% of patients with RA, are highly specific for the disease, and may be of value for both the diagnosis and the prognosis of RA. The fact that these antibodies may appear before the onset of the disease suggests a potential role in primary prevention. Interestingly, they may also play a role in the pathophysiology of this disabling disease. The process of citrullination, its physiologic role, and citrullination-related pathologies, as well as the use of anti-citrullinated protein antibody tests (ACPA) for the early diagnosis and prognosis of RA and their potential role in the pathophysiology of the disease, are discussed.