Analysis of autoantibodies to plasminogen in the serum of patients with rheumatoid arthritis.

Sera from patients with rheumatoid arthritis containing high titers of anti-streptokinase antibodies were found to contain anti-plasminogen antibodies of the IgG and IgA classes. High titers of anti-plasminogen autoantibodies of the IgA class were also found in sera from patients with systemic lupus erythematosus and Sjögren syndrome. Studies of the immune response to thrombolytic therapy with streptokinase in patients with no prior history of autoimmune disease suggest a strong correlation between streptokinase administration and the appearance of autoantibodies to plasminogen of the IgA class. The IgA anti-plasminogen autoantibody is specific for an epitope in a region of plasminogen which binds streptokinase and the IgG autoantibody reacts with an epitope in the C-terminal region corresponding to the catalytic domain of the plasminogen zymogen. Our findings suggest a different origin for the two classes of anti-plasminogen immunoglobulins in rheumatoid arthritis patients. Since plasminogen binding to rheumatoid synovial fibroblasts is enhanced, the high titers of both classes of anti-plasminogen autoantibodies may add to the localization and perpetuation of the immune response. We suggest that plasminogen may be a target of the immune response in autoimmune disease.