Human monoclonal antibodies against the complex of phosphatidylserine and prothrombin from patients with the antiphospholipid antibodies.
The presence of antibodies against the complex of prothrombin and phosphatidylserine (aPS/PT) more significantly correlates with manifestations of antiphospholipid syndrome (APS) and with the presence of lupus anticoagulants (LA) than antibodies against prothrombin bound to oxygenated polystyrene (aPT-A). To investigate immunological specificities and functional activities of aPS/PT, four monoclonal aPS/PT, designated as HG-4, KE-6, KF-5 and KF-6, from two patients with antiphospholipid antibodies (aPL) were established and characterized. Three of these antibodies (HG-4, KF-5 and KF-6) recognized the complex of phosphatidylserine and prothrombin, but did not react to prothrombin directly coated on oxygenated plates. KE-6 bound not only to the complex of phosphatidylserine and prothrombin but also to prothrombin on oxygenated plates. None of them showed the binding activity to prothrombin directly coated on non-oxygenated plates. HG-4, KE-6 and KF-5 had LA-like activity. The findings support the hypothesis that autoimmune aPS/PT recognize the cryptic epitopes or neoepitopes exposed upon interaction between prothrombin and phosphatidylserine, and that aPS/PT are, at least in part, responsible for LA activity.
Department of Medicine , Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan. thorita@med.hokudai.ac.jp
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Horita
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Ichikawa
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Kataoka
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Yasuda
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Atsumi
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Koike
D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000276:immunology*; D011379:Prognosis; D011516:Prothrombin / Q000276:immunology*; D012720:Severity of Illness Index
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D010718:Phosphatidylserines; D011516:Prothrombin