Rheumatoid arthritis (RA) is generally considered to be an autoimmune disease, as signified by the occurrence of autoreactive T lymphocytes and antibodies. The best known autoantigen in RA is the IgG isotype, which becomes the target of other antibodies, designated rheumatoid factors (RFs). The RF is currently the only serologic measure for RA included in the American College of Rheumatology criteria (1). It is still a matter of debate whether the production of RFs is of pathologic relevance to RA, since RF production also frequently occurs in patients with systemic lupus erythematosus (SLE), Sjögren’s syndrome, endocarditis, and liver diseases and even in healthy individuals. Furthermore, the quantity of RF production is not correlated with the clinical and serologic activity of RA and joint destruction. Autoantibodies in general have been shown to be pathogenic in such diseases as SLE, but the significance of autoantibodies and autoreactive T cells in RA remains unclear.

Although the mechanisms leading to the development of autoreactivity remain unknown, more and more autoantigens are described as novel targets in RA. Some autoantigens are well characterized biochemically and by their antigenic character, others are only poorly described and poorly understood. At the time of discovery some autoantibodies were rather appealing as targets because their B cell and/or T cell responses seemed to be highly specific for RA. Attention dropped rapidly after learning that these antibodies were present in other autoimmune diseases as well.