Βeta-2-glycoprotein I exerts antithrombotic function through its domain V in mice. Issue 126 (January 2022)

• Record Type: Journal Article
• Authors: Passam, Freda H.; Chen, Gang; Chen, Vivien M.; Qi, Miao; Krilis, Steven A.; Giannakopoulos, Bill
• Is Part Of: Journal of autoimmunity. Issue 126(2021)
• Publication Date: 2022-01
• Subjects: Beta 2 glycoprotein I -- Platelets -- Neutrophils -- Thrombosis -- Inflammation -- In vivo models; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2021.102747
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Little is known about the physiological role of beta-2-glycoprotein I (β2GPI) despite it being the major auto-antigen in the antiphospholipid syndrome. A systematic study of the role of β2GPI in thrombus formation in vivo has not been performed to date. Herein, we report that β2GPI deficient (−/−) mice have enhanced thrombus formation compared to wild type (WT) mice in a laser-induced arteriole and venule model of thrombosis. Furthermore, neutrophil accumulation and elastase activity was enhanced in thrombi of β2GPI −/− compared with WT mice. The antithrombotic function of β2GPI is dependent on its fifth domain (domain V); intravenous administration of the β2GPI domain deletion mutant lacking domain V (human recombinant domain I-IV) had no effect on platelet and fibrin thrombus size in β2GPI −/− or WT mice. On the contrary, intravenous administration of human recombinant domain V significantly inhibited platelet and fibrin thrombus size in both β2GPI −/− mice and WT mice. These findings reveal a major role for β2GPI as a natural anticoagulant and implicate domain V of β2GPI as a potential antithrombotic therapy. Highlights: Deficiency of β2GPI increases thrombosis and neutrophil recruitment in vivo in a laser-injury model of thrombosis. Inhibition of thrombosis by β2GPI is dependent on its domain V. Domain V of β2GPI has potential as an antithrombotic treatment.