PMID- 9649198
OWN - NLM
STAT- MEDLINE
DCOM- 19980720
LR  - 20190512
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 112
IP  - 2
DP  - 1998 May
TI  - Binding of anticardiolipin antibodies to protein C via beta2-glycoprotein I 
      (beta2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid 
      antibodies on the protein C system.
PG  - 325-33
AB  - 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 beta2-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 beta2-GPI by ELISA 
      (anti-'protein C' antibody ELISA), and compared their binding with those obtained 
      in the absence of beta2-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 
      beta2-GPI, but binding was not found in the absence of beta2-GPI. Highly 
      significant correlations were found between the titre of anti-'protein C' 
      antibody in the presence of beta2-GPI and that of anti-beta2-GPI antibody (r = 
      0.802, P = 0.0001). We further analysed the interaction between protein C, 
      phospholipids, beta2-GPI and human aCL MoAbs established from patients with 
      antiphospholipid syndrome. In a first set of experiments, the binding of 
      beta2-GPI to protein C and its phospholipid dependency were investigated. 
      Beta2-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 beta2-GPI (virtually anti-beta2-GPI antibodies) was evaluated 
      in the presence of cardiolipin and beta2-GPI. All three human monoclonal aCL 
      bound to protein C in the presence of CL and beta2-GPI, whereas they did not in 
      the absence of either beta2-GPI or CL. These data suggest that protein C could be 
      a target of aCL by making a complex with CL and beta2-GPI, leading to protein C 
      dysfunction.
FAU - Atsumi, T
AU  - Atsumi T
AD  - Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London, UK.
FAU - Khamashta, M A
AU  - Khamashta MA
FAU - Amengual, O
AU  - Amengual O
FAU - Donohoe, S
AU  - Donohoe S
FAU - Mackie, I
AU  - Mackie I
FAU - Ichikawa, K
AU  - Ichikawa K
FAU - Koike, T
AU  - Koike T
FAU - Hughes, G R
AU  - Hughes GR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Antibodies, Anticardiolipin)
RN  - 0 (Antibodies, Antiphospholipid)
RN  - 0 (Apolipoproteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Protein C)
RN  - 0 (beta 2-Glycoprotein I)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies, Anticardiolipin/*immunology
MH  - Antibodies, Antiphospholipid/*immunology
MH  - Antiphospholipid Syndrome/immunology
MH  - Apolipoproteins/*immunology
MH  - Child
MH  - Female
MH  - Glycoproteins/*immunology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Partial Thromboplastin Time
MH  - Protein Binding
MH  - Protein C/*immunology
MH  - beta 2-Glycoprotein I
PMC - PMC1904974
EDAT- 1998/07/02 00:00
MHDA- 1998/07/02 00:01
PMCR- 1999/05/01
CRDT- 1998/07/02 00:00
PHST- 1998/07/02 00:00 [pubmed]
PHST- 1998/07/02 00:01 [medline]
PHST- 1998/07/02 00:00 [entrez]
PHST- 1999/05/01 00:00 [pmc-release]
AID - 10.1046/j.1365-2249.1998.00582.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 1998 May;112(2):325-33. doi: 10.1046/j.1365-2249.1998.00582.x.