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Lupus
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Effect of ß2glycoprotein I and human monoclonal anticardiolipin antibody on the protein S/C4b-binding protein system

T. Atsumi

Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital, London, UK

MA Khamashta

Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital, London, UK

Prj Ames

Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital, London, UK

K. Ichikawa

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

T. Koike

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

Grv Hughes

Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital, London, UK

The effect of ß2glycoprotein I (ß2GPI) and human monoclonal anticardiolipin antibody (aCL) on the protein S/C4b-binding protein (C4BP) system was evaluated. The binding of C4BP to protein S was assessed by ELISA in the presence of ß2GPI with/without human monoclonal aCL. ß2GPI downregulated the binding between S and C4BP significantly. Human monoclonal aCL abolished the ß2GPI inhibitory effect in a calcium (Ca++) independent fashion. In separate experiments, the reactivity of aCL towards protein S in the presence or absence of ß2GPI and cardiolipin was investigated. Monoclonal aCL bound to protein S only in the presence of a combination of ß2GPI and cardiolipin. This binding was Ca++ dependent. These findings suggest that human monoclonal aCL increases the affinity of C4BP for protein S, and that protein S may represent one of the targets for aCL when combined with ß2GPI and cardiolipin. Both issues may explain acquired free protein S deficiency and the attendant risk of thrombosis in patients with aCL.

Key Words: antiphospholipid antibody • antiphosolipid syndrome • coagulation • thrombosis

Lupus, Vol. 6, No. 4, 358-364 (1997)
DOI: 10.1177/096120339700600403


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