HUMAN HYBRIDOMAS IN THE ANALYSIS OF AUTOIMMUNE DISEASE

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Human hybridomas and their monoclonal autoantibody products will be used to seek potentially unifying features in the autoimmunity that occurs in different diseases. Tests for serological cross-reactivity and sharing of idiotypes will examine the possibility that a restricted number of clones is involved in diverse autoimmune responses. In addition, the hypothesis that auto-anti-idiotype antibody formation is important in these responses will be tested. B. Furie's laboratory will isolate anti-platelet producing hybridomas from patients with autoimmune thrombocytopenia. K. McAdam's laboratory will isolate monoclonal antibodies from patients with leprosy with high levels of circulating immunoglobulin and antinuclear antibody. D. Stollar's laboratory will isolate monoclonal antibodies, from patients with SLE and related diseases, that cross-react with nuclear and cell surface membrane antigens. In each laboratory, the corresponding antigens will be identified and mutual cross-reactions among nuclear, cell surface and bacterial antigens will be tested. Selected antibodies will be partially sequenced to determine whether there are recurrent patterns in the framework and first hypervariable regions of the various autoantibodies. R. Schwartz's laboratory will prepare xenogeneic anti-idiotype reagents and compare the above monoclonal antibodies for shared idiotype. His laboratory will also test for auto-anti-idiotype antibodies in both hybridoma cultures and in sera, and determine whether their concentrations fluctuate in relation to disease activity.