title: A thrombin-cross-reactive anticardiolipin antibody binds to and inhibits the anticoagulant function of activated protein C.
abstract: 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.
authors.affiliation: Medicine/Rheumatology, University of California, Los Angeles, CA 90095-1670, USA. hwangkk@ucla.edu
authors.forename: Kwan-Ki
authors.initials: KK
authors.lastname: Hwang
authors.forename: Cheng-De
authors.initials: CD
authors.lastname: Yang
authors.forename: Weihong
authors.initials: W
authors.lastname: Yan
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Grossman
authors.forename: Bevra H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Pojen P
authors.initials: PP
authors.lastname: Chen
mesh_terms: 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*
chemical_list: D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D011486:Protein C; D018046:Protein C Inhibitor; D013917:Thrombin