A thrombin-cross-reactive anticardiolipin antibody binds to and inhibits the anticoagulant function of activated protein C.
OBJECTIVE
To test the hypotheses that some thrombin-reactive anticardiolipin antibodies (aCL) may bind to protein C (PC) and/or activated PC (APC), and that some of the PC- and APC-reactive aCL may inhibit PC activation and/or the function of APC.


METHODS
We studied the reactivity of patient-derived monoclonal aCL with PC and APC. We examined the effects of the reactive antibodies on PC activation and on the activity of APC in plasma coagulation.


RESULTS
Five of 5 patient-derived, thrombin-reactive monoclonal aCL bound to PC and APC. In addition, 1 patient-derived monoclonal antiprothrombin antibody (APT) that displayed aCL activity and reacted with thrombin also bound to PC and APC. Of these 6 PC- and APC-reactive aCL/APT, all failed to inhibit PC activation, but 1 (CL15) shortened the plasma coagulation time in the presence of exogenous APC and thus inhibited the anticoagulant function of APC.


CONCLUSIONS
Most of the thrombin-reactive aCL in patients with antiphospholipid syndrome may bind to PC and APC. Of the APC-reactive aCL, some (like CL15) may inhibit the anticoagulant function of APC and are thus likely to be prothrombotic in the host.
Hwang
Kwan-Ki
KK
Medicine/Rheumatology, University of California, Los Angeles, CA 90095-1670, USA. hwangkk@ucla.edu
Yang
Cheng-De
CD
Yan
Weihong
W
Grossman
Jennifer M
JM
Hahn
Bevra H
BH
Chen
Pojen P
PP
D000595:Amino Acid Sequence; D017153:Antibodies, Anticardiolipin / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000915:Antibody Affinity; D000925:Anticoagulants / Q000276:immunology*; D001666:Binding Sites, Antibody; D003429:Cross Reactions / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011486:Protein C / Q000737:chemistry / Q000276:immunology*; D018046:Protein C Inhibitor / Q000276:immunology*; D013917:Thrombin / Q000737:chemistry / Q000276:immunology*
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D011486:Protein C; D018046:Protein C Inhibitor; D013917:Thrombin