title: Antibodies against the activated coagulation factor X (FXa) in the antiphospholipid syndrome that interfere with the FXa inactivation by antithrombin.
abstract: Antiphospholipid Ab have been shown to promote thrombosis and fetal loss in the antiphospholipid syndrome (APS). Previously, we found IgG anti-thrombin Ab in some APS patients that could interfere with inactivation of thrombin by antithrombin (AT). Considering that activated coagulation factor X (FXa) is homologous to thrombin in the catalytic domains and is also regulated primarily by AT, we hypothesized that some thrombin-reactive Ab may bind to FXa and interfere with AT inactivation of FXa. To test these hypotheses, we studied reactivity of eight patient-derived monoclonal IgG antiphospholipid Ab with FXa and the presence of IgG anti-FXa Ab in APS patients and investigated the effects of FXa-reactive mAb on AT inactivation of FXa. The results revealed that six of six thrombin-reactive IgG mAb bound to FXa and that the levels of plasma IgG anti-FXa Ab in 38 APS patients were significantly higher than those in 30 normal controls (p < 0.001). When the mean plus 3 SDs of the 30 normal controls was used as the cutoff, 5 of 38 APS patients (13.2%) had IgG anti-FXa Ab. Importantly, three of six FXa-reactive mAb significantly inhibited AT inactivation of FXa. Combined, these results indicate that anti-FXa Ab may contribute to thrombosis by interfering with the anticoagulant function of AT on FXa in some APS patients.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of California-Los Angeles, 1000 Veteran Avenue, Los Angeles, CA 90095, USA.
authors.forename: Yao-Hsu
authors.initials: YH
authors.lastname: Yang
authors.forename: Kwan-Ki
authors.initials: KK
authors.lastname: Hwang
authors.forename: John
authors.initials: J
authors.lastname: FitzGerald
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Grossman
authors.forename: Mihaela
authors.initials: M
authors.lastname: Taylor
authors.forename: Bevra H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Pojen P
authors.initials: PP
authors.lastname: Chen
mesh_terms: D000911:Antibodies, Monoclonal / Q000097:blood; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000276:immunology*; D000991:Antithrombins / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D005170:Factor X / Q000276:immunology; D015951:Factor Xa / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D013927:Thrombosis / Q000209:etiology / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000991:Antithrombins; D001323:Autoantibodies; D007074:Immunoglobulin G; D005170:Factor X; D015951:Factor Xa