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

Department of Health and Disability, Laboratory of Immunobiology, National Public Health Institute, Helsinki, Finland; Laboratory of Immunobiology, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland marja.puurunen{at}phks.fi

T Palosuo

Department of Health and Disability, Laboratory of Immunobiology, National Public Health Institute, Helsinki, Finland

R Lassila

Wihuri Research Institute, Helsinki, Finland

M Anttila

National Veterinary and Food Research Institute, Helsinki, Finland

O Vaarala

Department of Biochemistry, National Public Health Institute, Helsinki, Finland

Antibodies to prothrombin have been associated with venous and arterial thrombosis, and they cross-react with a structurally closely related protein plasminogen. We immunised 16 mice with human prothrombin and 15 mice with human plasminogen. Mice immunised with prothrombin developed cross-reactive antibodies to plasminogen (12/16), b2-glycoprotein I (4/16), tissue-type plasminogen activator (6/16) and cardiolipin (11/16). Mice immunised with plasminogen developed cross-reactive antibodies to prothrombin (8/15), tissue-type plasminogen activator (2/12) and cardiolipin (5/12). Functional effects of antibodies were examined. Immunisation with prothrombin induced lupus 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 observed. 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 time, and immunisation with plasminogen induces antibodies interfering with fibrinolysis.

Key Words: antiprothrombin antibodies • antiphospholipid antibodies • antiplasminogen antibodies • lupus anticoagulant • fibrinolysis

Lupus, Vol. 10, No. 2, 108-115 (2001)
DOI: 10.1191/096120301666980003


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