Βeta-2-glycoprotein I exerts antithrombotic function through its domain V in mice

Freda H Passam; Gang Chen; Vivien M Chen; Miao Qi; Steven A Krilis; Bill Giannakopoulos

doi:10.1016/j.jaut.2021.102747

Βeta-2-glycoprotein I exerts antithrombotic function through its domain V in mice

J Autoimmun. 2022 Jan:126:102747. doi: 10.1016/j.jaut.2021.102747. Epub 2021 Nov 15.

Authors

Freda H Passam¹, Gang Chen², Vivien M Chen³, Miao Qi², Steven A Krilis⁴, Bill Giannakopoulos⁵

Affiliations

¹ Faculty Medicine Health, University of Sydney, Sydney, Australia; Heart Research Institute, Sydney, Australia.
² Department of Infectious Disease, Immunology and Sexual Health, St George Hospital, University of New South Wales, Sydney, Australia.
³ Department of Haematology, Concord Hospital, Sydney, NSW, Australia; ANZAC Research Institute, University of Sydney, NSW, Australia.
⁴ Department of Infectious Disease, Immunology and Sexual Health, St George Hospital, University of New South Wales, Sydney, Australia; Department of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia. Electronic address: s.krilis@unsw.edu.au.
⁵ Department of Infectious Disease, Immunology and Sexual Health, St George Hospital, University of New South Wales, Sydney, Australia; Department of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia. Electronic address: bill.giannakopoulos@unsw.edu.au.

PMID: 34794103
DOI: 10.1016/j.jaut.2021.102747

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.

Keywords: Beta 2 glycoprotein I; In vivo models; Inflammation; Neutrophils; Platelets; Thrombosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anticoagulants
Antiphospholipid Syndrome* / drug therapy
Antiphospholipid Syndrome* / genetics
Fibrinolytic Agents
Mice
Mice, Knockout
Thrombosis*
beta 2-Glycoprotein I* / physiology

Substances

Anticoagulants
Fibrinolytic Agents
beta 2-Glycoprotein I