New perspectives on the pathogenesis of rheumatoid arthritis.

In the pathogenesis of rheumatoid arthritis, locally produced antibodies complex with an inciting antigen, yet to be identified, within the joint and activate the complement system, resulting in articular inflammation mediated primarily by polymorphonuclear leukocytes and their products. Chronic inflammatory cells then produce soluble factors that induce both tissue destruction and inflammation. A major issue is how and why apparently normal immune responses in the acute stage progress to chronic inflammation in subsequent months to years. Although it is often assumed that the initial etiologic agent, persisting in the joint or at an extra-articular site, is responsible for continued synovitis, this need not be the case. It is possible that once the inciting agent is cleared from the joint through a normal immune response, the presence of activated cells rich in surface class II histocompatibility (Ia) antigens could, under the influence of multiple genetic or environmental factors, become the target of autoimmune attack. Alternatively, the process might result from the interactions of synovial lining cells and their products with T cells assuming a secondary role. Further research into the relative contributions of soluble products, T helper and suppressor subsets, synoviocytes, and antigen determine which model is correct.