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Lupus
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Human monoclonal antibodies against the complex of phosphatidylserine and prothrombin from patients with the antiphospholipid antibodies

T. Horita

Department of Medicine , Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan, thorita{at}med.hokudai.ac.jp

K. Ichikawa

Department of Medicine , Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan

H. Kataoka

Department of Medicine , Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan

S. Yasuda

Department of Medicine , Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan

T. Atsumi

Department of Medicine , Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan

T. Koike

Department of Medicine , Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan

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. Lupus (2007) 16, 509—516.

Key Words: antiphospholipid antibodies • lupus anticoagulant • monoclonal antibody • prothrombin • systemic lupus erythematosus

Lupus, Vol. 16, No. 7, 509-516 (2007)
DOI: 10.1177/0961203307078680
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