Increasing evidence indicates that immune mechanisms are involved in maintaining the chronic inflammation in patients with rheumatoid arthritis. Both the cellular and antibody arms of immunity are involved in this process. Studies are proposed to enhance the knowledge of humoral immunity in this disease process through studies on rheumatoid factors. Current knowledge indicates that these are the most common antibodies in the pathogenesis of inflammation in rheumatoid arthritis. Since previous studies have identified specific sites on IgG molecules to which both rheumatoid factors and certain microbial proteins bind, the significance of these findings will be explored. This will be achieved by identifying the prevalence of specific rheumatoid factors and by examining if these specific rheumatoid factors arise as anti-idiotypes to the antibodies to bacterial proteins. The idiotypes on rheumatoid factors and the presence of auto-anti-idiotype to rheumatoid factors will be investigated. Monoclonal IgG-rheumatoid factors from MRL/1 mice will be examined as a model for human rheumatoid factors. Since a unique feature of rheumatoid arthritis is the presence of abundant immlunoglobulins on joint cartilage, the nature of these molecules will be defined. This work will be accomplished with immunochemical and biochemical methods that are established in these laboratories. The used methods will include liquid-phase protein isolation methods, high performance liquid chromatography, affinity chromatography, radioimmunoassays, enzyme-linked immunosorben assays, immunofluorescence microscopy and cell hybridization. The specimens to be examined will be obtained from patients with rheumatoid arthritis. The results of the proposed investigations should substantially enhance the knowledge of the disease processes in patients with rheumatoid arthritis.
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