Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, N.C., USA.
Kidney Dis (Basel). 2016 Mar;1(4):205-15. doi: 10.1159/000442323. Epub 2015 Dec 3.
Antineutrophil cytoplasmic autoantibodies (ANCA) are associated with a spectrum of necrotizing vasculitis including granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited necrotizing and crescentic glomerulonephritis. Clinical observations and in vitro and in vivo experimental evidence strongly indicate that ANCA are pathogenic.
The etiology and pathogenesis of ANCA-associated vasculitis (AAV) are multifactorial, with contributions from genetic factors, environmental exposures, infections, characteristics of the innate and adaptive immune system, and the intensity and duration of the injury. Acute vascular inflammation is induced when resting neutrophils that have ANCA autoantigens sequestered in cytoplasmic granules are exposed to priming factors - for example, cytokines induced by infection or phlogogenic factors released by complement activation - that cause the release of ANCA antigens on the surface of neutrophils and in the microenvironment around the neutrophils. ANCA bind to these ANCA antigens, which activates neutrophils by Fcγ receptor engagement and F(ab')2 binding at the neutrophil cell surface. ANCA-activated neutrophils release factors that activate the alternative complement pathway, which generates C5a, a chemoattractant for neutrophils; C5a also primes the arriving neutrophils for activation by ANCA. Activated neutrophils adhere to and penetrate vessel walls, and they release toxic oxygen radicals and destructive enzymes that cause apoptosis and necrosis of the neutrophils as well as of the adjacent vessel wall cells and matrix.
Patients with active AAV have ongoing asynchronous onsets of countless acute lesions, with each lesion evolving through stereotypical phases within 1 or 2 weeks. Induction of remission results in termination of new waves of acute lesions and allows all lesions to progress to scarring or resolution.
抗中性粒细胞胞浆抗体 (ANCA) 与多种坏死性血管炎相关，包括肉芽肿性多血管炎、显微镜下多血管炎、嗜酸性肉芽肿性多血管炎和肾局限性坏死性和新月体性肾小球肾炎。临床观察和体外及体内实验证据强烈表明 ANCA 具有致病性。
抗中性粒细胞胞浆抗体相关性血管炎 (AAV) 的病因和发病机制是多因素的，涉及遗传因素、环境暴露、感染、固有和适应性免疫系统特征以及损伤的强度和持续时间。当静息的中性粒细胞中含有 ANCA 自身抗原的细胞质颗粒被暴露于启动因子（例如感染诱导的细胞因子或补体激活释放的趋化因子）时，就会诱导急性血管炎症，导致中性粒细胞表面和周围微环境中 ANCA 抗原的释放。ANCA 与这些 ANCA 抗原结合，通过 Fcγ 受体结合和 F(ab')2 在中性粒细胞表面的结合激活中性粒细胞。ANCA 激活的中性粒细胞释放激活替代补体途径的因子，该途径生成 C5a，一种中性粒细胞的趋化因子；C5a 还使到达的中性粒细胞通过 ANCA 被激活。激活的中性粒细胞黏附和穿透血管壁，并释放有毒的氧自由基和破坏性酶，导致中性粒细胞以及相邻血管壁细胞和基质的凋亡和坏死。
患有活动性 AAV 的患者有无数急性病变的持续异步发作，每个病变在 1 或 2 周内通过典型阶段进展。诱导缓解可导致新一波急性病变的终止，并使所有病变进展为瘢痕或消退。
