Open AccessBinding of anticardiolipin antibodies to protein C via β 2 ‐glycoprotein I (β 2 ‐GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system
Author(s) -
Tatsuya Atsumi,
Munther Khamashta,
Olga Amengual,
S Donohoe,
Ian Mackie,
Kenji Ichikawa,
Takao Koike,
G. R. V. Hughes
Publication year - 1998
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1998.00582.x
Subject(s) - cardiolipin , epitope , antibody , phosphatidylserine , antiphospholipid syndrome , autoantibody , monoclonal antibody , microbiology and biotechnology , biology , binding protein , immunology , chemistry , biochemistry , phospholipid , gene , membrane
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 β 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 β 2 ‐GPI by ELISA (anti‐‘protein C’ antibody ELISA), and compared their binding with those obtained in the absence of β 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 β 2 ‐GPI, but binding was not found in the absence of β 2 ‐GPI. Highly significant correlations were found between the titre of anti‐‘protein C’ antibody in the presence of β 2 ‐GPI and that of anti‐β 2 ‐GPI antibody ( r = 0.802, P = 0.0001). We further analysed the interaction between protein C, phospholipids, β 2 ‐GPI and human aCL MoAbs established from patients with antiphospholipid syndrome. In a first set of experiments, the binding of β 2 ‐GPI to protein C and its phospholipid dependency were investigated. β 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 β 2 ‐GPI (virtually anti‐β 2 ‐GPI antibodies) was evaluated in the presence of cardiolipin and β 2 ‐GPI. All three human monoclonal aCL bound to protein C in the presence of CL and β 2 ‐GPI, whereas they did not in the absence of either β 2 ‐GPI or CL. These data suggest that protein C could be a target of aCL by making a complex with CL and β 2 ‐GPI, leading to protein C dysfunction.