Complement and thrombosis in the antiphospholipid syndrome

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• 作者：Kenji Oku ; ^{kenoku@med.hokudai.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Hiroyuki Nakamura ; Michihiro Kono ; Kazumasa Ohmura ; Masaru Kato ; Toshiyuki Bohgaki ; Tetsuya Horita ; Shinsuke Yasuda ; Olga Amengual ; Tatsuya Atsumi
• 关键词：Antiphospholipid syndrome ; Anti-C1q antibody ; Complement pathway ; Antiphospholipid antibody
• 刊名：Autoimmunity Reviews
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：15
• 期：10
• 页码：1001-1004
• 全文大小：311 K

文摘

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.