title: Complement and thrombosis in the antiphospholipid syndrome.
abstract: The involvement of complement activation in the pathophysiology of antiphospholipid syndrome (APS) was first reported in murine models of antiphospholipid antibody (aPL)-related pregnancy morbidities. We previously reported that complement activation is prevalent and may function as a source of procoagulant cell activation in the sera of APS patients. Recently, autoantibodies against C1q, a component of complement 1, were reported to be correlated with complement activation in systemic lupus erythematosus. These antibodies target neoepitopes of deformed C1q bound to various molecules (i.e., anionic phospholipids) and induce accelerated complement activation. We found that anti-C1q antibodies are more frequently detected in primary APS patients than in control patients and in refractory APS patients with repeated thrombotic events. The titer of anti-C1q antibodies was significantly higher in refractory APS patients than in APS patients without flare. The binding of C1q to anionic phospholipids may be associated with the surge in complement activation in patients with anti-C1q antibodies when triggered by 'second-hit' biological stressors such as infection. Such stressors will induce overexpression of anionic phospholipids, with subsequent increases in deformed C1q that is targeted by anti-C1q antibodies.
authors.affiliation: Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. Electronic address: kenoku@med.hokudai.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Oku
authors.affiliation: Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kono
authors.affiliation: Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ohmura
authors.affiliation: Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Bohgaki
authors.affiliation: Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Horita
authors.affiliation: Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Olga
authors.initials: O
authors.lastname: Amengual
authors.affiliation: Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
mesh_terms: D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D013927:Thrombosis / Q000097:blood / Q000276:immunology* / Q000473:pathology
chemical_list: D017152:Antibodies, Antiphospholipid; D003165:Complement System Proteins
keywords: Anti-C1q antibody; Antiphospholipid antibody; Antiphospholipid syndrome; Complement pathway