title: The Fifth Domain of Beta 2 Glycoprotein I Protects from Natural IgM Mediated Cardiac Ischaemia Reperfusion Injury.
abstract: Reperfusion after a period of ischemia results in reperfusion injury (IRI) which involves activation of the inflammatory cascade. In cardiac IRI, IgM natural antibodies (NAb) play a prominent role through binding to altered neoepitopes expressed on damaged cells. Beta 2 Glycoprotein I (β2GPI) is a plasma protein that binds to neoepitopes on damaged cells including anionic phospholipids through its highly conserved Domain V. Domain I of β2GPI binds circulating IgM NAbs and may provide a link between the innate immune system, IgM NAb binding and cardiac IRI. This study was undertaken to investigate the role of Β2GPI and its Domain V in cardiac IRI using wild-type (WT), Rag-1 -/- and β2GPI deficient mice. Compared with control, treatment with Domain V prior to cardiac IRI prevented binding of endogenous β2GPI to post-ischemic myocardium and resulted in smaller myocardial infarction size in both WT and β2GPI deficient mice. Domain V treatment in WT mice also resulted in less neutrophil infiltration, less apoptosis and improved ejection fraction at 24 h. Rag-1 -/- antibody deficient mice reconstituted with IgM NAbs confirmed that Domain V prevented IgM NAb induced cardiac IRI. Domain V remained equally effective when delivered at the time of reperfusion which has therapeutic clinical relevance.Based upon this study Domain V may function as a universal inhibitor of IgM NAb binding in the setting of cardiac IRI, which offers promise as a new therapeutic strategy in the treatment of cardiac IRI.
authors.affiliation: Department of Infectious Diseases, Immunology and Sexual Health, St George Hospital, Sydney, Australia.|Department of Medicine, University of New South Wales, Sydney, Australia.|Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Immunology and Sexual Health, St George Hospital, Sydney, Australia.|Department of Medicine, University of New South Wales, Sydney, Australia.|Department of Cardiology, St George Hospital, Sydney, Australia.
authors.forename: James C
authors.initials: JC
authors.lastname: Weaver
authors.affiliation: Department of Infectious Diseases, Immunology and Sexual Health, St George Hospital, Sydney, Australia.|Department of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Anatomical Pathology, SEALS St George Hospital, Sydney, Australia.
authors.forename: Julia
authors.initials: J
authors.lastname: Beretov
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.affiliation: Department of Infectious Diseases, Immunology and Sexual Health, St George Hospital, Sydney, Australia.|Department of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Miao
authors.initials: M
authors.lastname: Qi
authors.affiliation: Department of Cardiology, Royal North Shore Hospital, Sydney, Australia.
authors.forename: Ravinay
authors.initials: R
authors.lastname: Bhindi
authors.affiliation: Department of Infectious Diseases, Immunology and Sexual Health, St George Hospital, Sydney, Australia.|Department of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Jian C
authors.initials: JC
authors.lastname: Qi
authors.affiliation: Save Sight Institute, University of Sydney and Sydney Eye Hospital, Sydney, Australia.|School of Optometry and Vision Science, University of New South Wales, Sydney, Australia.
authors.forename: Michele C
authors.initials: MC
authors.lastname: Madigan
authors.affiliation: Department of Infectious Diseases, Immunology and Sexual Health, St George Hospital, Sydney, Australia.|Department of Medicine, University of New South Wales, Sydney, Australia.|Department of Rheumatology, St George Hospital, Sydney, Australia.
authors.forename: Bill
authors.initials: B
authors.lastname: Giannakopoulos
authors.affiliation: Department of Infectious Diseases, Immunology and Sexual Health, St George Hospital, Sydney, Australia.|Department of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Krilis
mesh_terms: D000818:Animals; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics; D007075:Immunoglobulin M / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D017434:Protein Structure, Tertiary; D053482:beta 2-Glycoprotein I / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
chemical_list: D007075:Immunoglobulin M; D053482:beta 2-Glycoprotein I