BINDING OF ANTICARDIOLIPIN ANTIBODIES TO PROTEIN-C VIA BETA(2)-GLYCOPROTEIN-I (BETA(2)-GPI) - A POSSIBLE MECHANISM IN THE INHIBITORY EFFECTOF ANTIPHOSPHOLIPID ANTIBODIES ON THE PROTEIN-C SYSTEM
T. Atsumi et al., BINDING OF ANTICARDIOLIPIN ANTIBODIES TO PROTEIN-C VIA BETA(2)-GLYCOPROTEIN-I (BETA(2)-GPI) - A POSSIBLE MECHANISM IN THE INHIBITORY EFFECTOF ANTIPHOSPHOLIPID ANTIBODIES ON THE PROTEIN-C SYSTEM, Clinical and experimental immunology, 112(2), 1998, pp. 325-333
It is known that antiphospholipid antibodies (aPL) hamper the anticoag
ulant activity of the protein C system, but the mechanism is still obs
cure. In this study, we demonstrate that anticardiolipin antibodies (n
ot anti-protein C autoantibodies) can bind protein C via beta(2)-GPI,
which bears their binding epitope, in a fashion dependent on negativel
y charged phospholipids. We studied the binding of IgG from aPL to pro
tein C in the presence of beta(2)-GPI by ELISA (anti-'protein C' antib
ody ELISA), and compared their binding with those obtained in the abse
nce of beta(2)-GPI. In the anti-'protein C' antibody ELISA system, 47%
of 78 aPL(+) patients had a positive titre in the presence oi cardiol
ipin (CL) and beta(2)-GPI, but binding was not found in the absence of
beta(2)-GPI. Highly significant correlations were found between the t
itre of anti-'protein C' antibody in the presence of beta(2)-GPI and t
hat of anti-beta(2)-GPI antibody (r=0.802, P = 0.0001). We further ana
lysed the interaction between protein C, phospholipids, beta(2)-GPI an
d human aCL MoAbs established from patients with antiphospholipid synd
rome. In a first set of experiments, the binding of beta(2)-GPI to pro
tein C and its phospholipid dependency were investigated. beta(2)-GPI
bound to protein C in the presence of CL or phosphatidylserine, but no
t in the presence of phosphatidylcholine or phosphatidylethanolamine.
In a second group of experiments, the binding of three human monoclona
l aCL recognizing the cryptic epitope of beta(2)-GPI (virtually anti-b
eta(2)-GPI antibodies) was evaluated in the presence of cardiolipin an
d beta(2)-GPI. All three human monoclonal aCL bound to protein C in th
e 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 b
e a target of aCL by making a complex with CL and beta(2)-GPI, leading
to protein C dysfunction.