Pathogenesis of rheumatoid arthritis

Although widely diverse mechanisms have been held responsible for tissue damage in rheumatoid arthritis (RA), it is likely that immune complexes are the underlying cause. Self-aggregating complexes of 7s rheumatoid factors in synovial fluid are a distinguishing feature of RA, whilst circulating complexes of 19s rheumatoid factor directed against the hinge region of 7s immunoglobulins are perhaps less specific. Other autoimmune complexes, such as those containing antibodies directed against citrullinated peptides, have been identified and may be more specific for RA, although the antigens against which these antibodies are directed have not been fully characterized. Together with phagocytic cells such as neutrophils, immune complexes are critical to the pathogenesis of RA; their effects are mediated by a complex cascade involving complement activation and stimulation of phagocytes via C5a and Fc receptors. These mechanisms result in a release of mediators of inflammation and joint destruction: cytokines, metalloproteinases, and reactive oxygen intermediates. This article will review recent, and some not too recent, progress made towards working out the pathogenesis of RA.