UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Binding of anticardiolipin antibodies to protein C via beta(2)-glycoprotein I (beta(2)-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system

Atsumi, T; Khamashta, MA; Amengual, O; Donohoe, S; Mackie, I; Ichikawa, K; Koike, T; (1998) Binding of anticardiolipin antibodies to protein C via beta(2)-glycoprotein I (beta(2)-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system. CLIN EXP IMMUNOL , 112 (2) 325 - 333.

Full text not available from this repository.

Abstract

It is known that antiphospholipid antibodies (aPL) hamper the anticoagulant activity of the protein C system, but the mechanism is still obscure. In this study, we demonstrate that anticardiolipin antibodies (not anti-protein C autoantibodies) can bind protein C via beta(2)-GPI, which bears their binding epitope, in a fashion dependent on negatively charged phospholipids. We studied the binding of IgG from aPL to protein C in the presence of beta(2)-GPI by ELISA (anti-'protein C' antibody ELISA), and compared their binding with those obtained in the absence of beta(2)-GPI. In the anti-'protein C' antibody ELISA system, 47% of 78 aPL(+) patients had a positive titre in the presence of cardiolipin (CL) and beta(2)-GPI, but binding was not found in the absence of beta(2)-GPI. Highly significant correlations were found between the titre of anti-'protein C' antibody in the presence of beta(2)-GPI and that of anti-beta(2)-GPI antibody (r=0.802, P = 0.0001). We further analysed the interaction between protein C, phospholipids, beta(2)-GPI and human aCL MoAbs established from patients with antiphospholipid syndrome. In a first set of experiments, the binding of beta(2)-GPI to protein C and its phospholipid dependency were investigated. beta(2)-GPI bound to protein C in the presence of CL or phosphatidylserine, but not in the presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of experiments, the binding of three human monoclonal aCL recognizing the cryptic epitope of beta(2)-GPI (virtually anti-beta(2)-GPI antibodies) was evaluated in the presence of cardiolipin and beta(2)-GPI. All three human monoclonal aCL bound to protein C in the presence of CL and beta(2)-GPI, whereas they did not in the absence of either beta(2)-GPI or CL. These data suggest that protein C could be a target of aCL by making a complex with CL and beta(2)-GPI, leading to protein C dysfunction.

Type: Article
Title: Binding of anticardiolipin antibodies to protein C via beta(2)-glycoprotein I (beta(2)-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system
Keywords: thrombosis, antiphospholipid syndrome, coagulation, phospholipid-binding protein, THROMBIN-CATALYZED ACTIVATION, FACTOR-VA INACTIVATION, COAGULATION FACTOR-V, LUPUS-ERYTHEMATOSUS, ENDOTHELIAL-CELLS, BLOOD-COAGULATION, GLYCOPROTEIN-I, RECOGNIZE BETA(2)-GLYCOPROTEIN-I, C4B-BINDING PROTEIN, S DEFICIENCY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1324288
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item