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

Abstract

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.

Heat Shock Protein and Gliadin Peptide Promote Development of Peptidase Antibodies in Children with Autism and Patients with Autoimmune Disease

“…DPP IV is a receptor for streptokinase (SK) on rheumatoid synovial fibroblasts via the LTSRPA amino acid sequence (18). Binding of SK, the bacterial protein, to DPP IV resulted in the appearance of anti-SK and anti-DPP IV autoantibodies in patients with myocardial infarction treated with SK (8,19). Based on these observations and the potent immunogenicity of SK in patients with autoimmune disease, SK could bind to DPP IV and induce significant levels of anti-SK and anti-DPP IV antibody production.…”

Immunologic and hematologic properties of antibodies to prothrombin and plasminogen in a mouse model

“…In humans antibodies to plasminogen have been described in rheumatoid arthritis and reactive arthritis 30 and in patients with SLE and Sjo Ègren's syndrome. 31 Their role in pathophysiology of the diseases and effect on ®brinolysis remains unclear.…”

Autoantibodies to plasminogen and tissue plasminogen activator in women with recurrent pregnancy loss

“…1). The presence of IgG anti-PLG has been reported in patients with rheumatoid arthritis and SLE, and it was suggested that PLG may be a target of the immune response in autoimmune disease [12][13][14]. The association of anti-t-PA antibodies with thrombosis was also reported to be related to APS [17,18].…”

“…It is unclear whether antibodies to PLG and t-PA are directly pathogenic, a result of the pregnancy losses or markers for an underlying and uncharacterized autoimmune disorder. The presence of anti-PLG antibody in patients with rheumatoid arthritis and systemic lupus erythematosus (SLE) was reported, and it was suggested that PLG might be a target of the immune response in autoimmune disease [12][13][14]. However, controversy exists with regard to the clinical significance of anti-PLG antibodies in patients with autoimmune diseases.…”