Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
University of North Carolina Kidney Center, Chapel Hill, North Carolina.
Semin Respir Crit Care Med. 2018 Aug;39(4):413-424. doi: 10.1055/s-0038-1673386. Epub 2018 Nov 7.
Antineutrophil cytoplasmic antibodies (ANCAs) are autoantibodies specific for antigens located in the cytoplasmic granules of neutrophils and lysosomes of monocytes. ANCAs are associated with a spectrum of necrotizing vasculitis that includes granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. Pulmonary vasculitis and related extravascular inflammation and fibrosis are frequent components of ANCA vasculitis. In this review, we detail the factors that have been associated with the origin of the ANCA autoimmune response and summarize the most relevant clinical observations, in vitro evidence, and animal studies strongly indicating the pathogenic potential of ANCA. In addition, we describe the putative sequence of pathogenic mechanisms driven by ANCA-induced activation of neutrophils that result in small vessel necrotizing vasculitis and extravascular granulomatous necrotizing inflammation.
抗中性粒细胞胞浆抗体 (ANCA) 是针对中性粒细胞细胞质颗粒和单核细胞溶酶体中抗原的自身抗体。ANCA 与一系列坏死性血管炎有关，包括肉芽肿性多血管炎、显微镜下多血管炎和嗜酸性肉芽肿性多血管炎。肺血管炎及相关的血管外炎症和纤维化是 ANCA 血管炎的常见组成部分。在这篇综述中，我们详细描述了与 ANCA 自身免疫反应起源相关的因素，并总结了最相关的临床观察、体外证据和动物研究，这些研究强烈表明了 ANCA 的致病潜力。此外，我们还描述了由 ANCA 诱导的中性粒细胞激活引起的致病机制的假设序列，这些机制导致小血管坏死性血管炎和血管外肉芽肿性坏死性炎症。
