Use and significance of anti-CCP autoantibodies in rheumatoid arthritis

One of the most common autoimmune diseases is rheumatoid arthritis (RA), affecting 0.5–1% of the population. This systemic disease is marked by chronic inflammation of synovial joints, which leads to destruction of cartilage and bone and eventually to disability of the patient [1]. Though not directly lifethreatening, RA severely affects the quality of life of a patient and also has major economic consequences for society. Therefore, every attempt should be made to prevent the erosive processes to occur. Currently, the classification of RA relies mainly on the criteria described by the American College of Rheumatology (ACR) [2]. These criteria, originally formulated 50 yr ago and last adjusted in 1987, are based mainly on clinical parameters. Since these parameters are often only sufficiently fulfilled when the damaging effects of the inflammatory process are already in progress, this set of criteria is not very suitable for the early diagnosis of RA [3]. The key to early recognition of autoimmunity lies within the humoral immune system. Since blood samples are taken from clinic-visiting (pre-)patients, screening for serological RA-indicators can be performed quite easily. In the ACR criteria for RA one serological marker is included: rheumatoid factor (RF). The RF autoantibody system, directed against the Fc part of immunoglobulin (Ig) G molecules, has had a central role in the diagnosis and prognosis of RA during recent decades [4] because RF can be detected in the majority of RA patients. However, it is becoming more and more clear that the presence of RF is not restricted to patients with RA, but that it can also be detected in subsets of patients suffering from other diseases and even in a percentage of healthy (especially elderly) individuals [5]. The resulting lack of specificity for RA can lead to confusion and unwanted treatment. The shortcomings of the RF test have kept the search for more specific RA markers alive. Most autoantibody systems described during recent decades have failed to mature into mainstream tests for RA because of low sensitivity, lack of specificity or technical inconvenience, as reviewed previously [6–8]. The only antibody system that combines good sensitivity with superior specificity for RA is that targeting citrullinated epitopes. This review will focus mainly on the diagnostic potential of the second-generation anti-cyclic citrullinated peptide (CCP) test (CCP2) for RA. Next, we will address the prognostic ability of the anti-CCP test. The presence of these antibodies early in disease development opens a window of opportunity for early custom-tailored treatment of RA. Finally, we will review the effect of disease treatment on anti-CCP levels and briefly go into the putative functional role of these antibodies in the chronic aspects of RA.