Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, P. R. China.
Department of Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, Cambridge, UK.
Nat Rev Nephrol. 2017 Jun;13(6):359-367. doi: 10.1038/nrneph.2017.37. Epub 2017 Mar 20.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of potentially life-threatening autoimmune diseases. The main histological feature in the kidneys of patients with AAV is pauci-immune necrotizing crescentic glomerulonephritis with little immunoglobulin and complement deposition in the glomerular capillary walls. The complement system was not, therefore, initially thought to be associated with the development of AAV. Accumulating evidence from animal models and clinical observations indicate, however, that activation of the complement system - and the alternative pathway in particular - is crucial for the development of AAV, and that the complement activation product C5a has a central role. Stimulation of neutrophils with C5a and ANCA not only results in the neutrophil respiratory burst and degranulation, but also activates the coagulation system and generates thrombin, thus bridging the inflammation and coagulation systems. In this Review, we provide an overview of the clinical, in vivo and in vitro evidence for a role of complement activation in the development of AAV and discuss how targeting the complement system could provide opportunities for therapy.
抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）是一组潜在威胁生命的自身免疫性疾病。AAV 患者肾脏的主要组织学特征是少免疫性坏死性新月体肾小球肾炎，肾小球毛细血管壁内很少有免疫球蛋白和补体沉积。因此，补体系统最初并未被认为与 AAV 的发生有关。然而，来自动物模型和临床观察的越来越多的证据表明，补体系统的激活——特别是替代途径——对于 AAV 的发生至关重要，补体激活产物 C5a 起着核心作用。C5a 和 ANCA 刺激中性粒细胞不仅导致中性粒细胞呼吸爆发和脱颗粒，还激活凝血系统并产生凝血酶，从而将炎症和凝血系统联系起来。在这篇综述中，我们概述了补体激活在 AAV 发生中的作用的临床、体内和体外证据，并讨论了如何针对补体系统为治疗提供机会。
