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

Antibodies to prothrombin have been associated with venous and arterial thr ombosis, and they cross-react with a structurally closely related protein p lasminogen. We immunised 16 mice with human prothrombin and 15 mice with hu man plasminogen. Mice immunised with prothrombin developed cross-reactive a ntibodies to plasminogen (12/16), beta2-glycoprotein I (4/16), tissue-type plasminogen activator (6/16) and cardiolipin (11/16). Mice immunised with p lasminogen developed cross-reactive antibodies to prothrombin (8/15), tissu e-type plasminogen activator (2/12) and cardiolipin (5/12). Functional effe cts of antibodies were examined. Immunisation with prothrombin induced lupu s anticoagulant activity in 9/14 mice. In mice immunised with plasminogen, radial fibrinolysis was inhibited in 8/10 and plasminogen activation in the chromogenic assay was inhibited in 9/11. No cross-functionality was observ ed. In conclusion, antibodies to prothrombin and plasminogen cross-react in vivo. Antibodies to prothrombin and plasminogen have different functional profiles, immunisation with prothrombin leads to prolonged blood clotting t ime, and immunisation with plasminogen induces antibodies interfering with fibrinolysis.