补体活化旁路途经在抗中性粒细胞胞质抗体相关性血管炎发病机制中作用的研究进展

Research advance of alternative complement pathway in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitides

抗中性粒细胞胞质抗体(ANCA)相关性血管炎(AAV)是一组与环境、遗传及自身免疫等多因素有关的系统性疾病,常导致患者死亡。因AAV的肾损害病理检查多显示为寡或无明显免疫复合物沉积,虽然有证据显示ANCA参与AAV的发病,但免疫复合物及补体系统活化在AAV发病中的作用长期未被重视。近10余年来,越来越多的病理、动物实验及临床研究证据,提示补体活化旁路途经在AAV的发病中发挥关键作用,尤其是C5a在AAV的病理损害中的作用成为研究热点,对C5a及C5a受体在AAV发病中作用的深入探讨,不仅进一步提示补体旁路途经参与AAV的发病,而且为临床治疗AAV提供潜在的靶点途经。

Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a life-threatening form of auto-immune small-vessel vasculitis, which is thought to be related to environment, genetic, autoimmunity and so on. Although it is identified that complement is crucial in the pathogenesis of AAV, ANCA glomerulonephritis has comparatively much less complement detected by immunofluorescence microscopy in involved vessels. So complement initially is not envisioned as an important participant in the pathogenesis of AAV. In recent years, more and more evidences on pathology, animal experiments, clinical studies confirm that alternative complement pathway plays a critical role in the pathogenesis of AAV, especially complement C5a becomes the hotspot of researches. Along with the depth exploration of C5a and C5a receptor in the pathogenesis of AAV, we can not only prove that alternative complement pathway is crucial in the pathogenesis of AAV, but also find the potential targets to AAV clinical treatment.