Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Autoimmun Rev. 2016 Oct;15(10):1001-4. doi: 10.1016/j.autrev.2016.07.020. Epub 2016 Jul 30.
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.
补体激活参与抗磷脂综合征（APS）的病理生理学过程最早在抗磷脂抗体（aPL）相关妊娠并发症的鼠模型中报道。我们之前报道过，补体激活在 APS 患者的血清中很常见，可能作为促凝细胞激活的来源。最近，报道称针对补体 1 成分 C1q 的自身抗体与系统性红斑狼疮中的补体激活相关。这些抗体针对与各种分子（即阴离子磷脂）结合的变形 C1q 的新表位，并诱导加速的补体激活。我们发现，与对照组患者相比，原发性 APS 患者和复发性血栓事件的难治性 APS 患者中更频繁地检测到抗 C1q 抗体。与无复发的 APS 患者相比，难治性 APS 患者的抗 C1q 抗体滴度显著更高。当 C1q 与阴离子磷脂的结合被“二次打击”生物应激源（如感染）触发时，可能与抗 C1q 抗体患者补体激活的激增有关。这种应激源会诱导阴离子磷脂的过度表达，随后增加被抗 C1q 抗体靶向的变形 C1q。
