Departments of *Pathology and Laboratory Medicine †Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
Adv Anat Pathol. 2017 Jul;24(4):226-234. doi: 10.1097/PAP.0000000000000154.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized as inflammation of small-sized to medium-sized blood vessels and encompasses several clinicopathologic entities including granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited ANCA-associated vasculitis. Over the past several decades, significant progress has been made in understanding the pathophysiology of ANCA-associated vasculitis. Although neutrophils contain a multitude of granular proteins, clinically significant autoantibodies are only recognized against myeloperoxidase and proteinase 3, both of which are present in the azurophilic granules. The propensity to develop these antibodies depends on a variety of predisposing factors such as microbial infection, genetic factors, environmental agents, and therapeutic drugs among others. These factors are usually associated with production of proinflammatory cytokines with capacity to prime the neutrophils. As a result a high proportion of neutrophils in circulation may be primed resulting in exposure of cytoplasmic proteins including myeloperoxidase and proteinase 3 on the surface of the neutrophils. Primed neutrophils are activated by interaction with ANCA in circulation. Activated neutrophils attach to and transmigrate through endothelium and accumulate within the vessel wall. These neutrophils degranulate and produce reactive oxygen radicals and ultimately die, causing tissue injury. Endothelial injury results in leakage of serum proteins and coagulation factors causing fibrinoid necrosis. B cells produce ANCAs, as well as neutrophil abnormalities and imbalances in different T-cell subtypes with excess of Th17, which perpetuate the inflammatory process.
抗中性粒细胞胞浆抗体（ANCA）相关性血管炎的特征是小至中等大小血管的炎症，包括几种临床病理实体，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性 ANCA 相关性血管炎。在过去的几十年中，人们在理解 ANCA 相关性血管炎的病理生理学方面取得了重大进展。虽然中性粒细胞含有多种颗粒蛋白，但临床上只有针对髓过氧化物酶和蛋白酶 3 的自身抗体具有重要意义，这两种蛋白都存在于嗜天青颗粒中。产生这些抗体的倾向取决于多种易感因素，如微生物感染、遗传因素、环境因素和治疗药物等。这些因素通常与产生能够激活中性粒细胞的促炎细胞因子有关。因此，循环中的中性粒细胞可能会被大量激活，导致包括髓过氧化物酶和蛋白酶 3 在内的细胞质蛋白暴露在中性粒细胞表面。被激活的中性粒细胞通过与循环中的 ANCA 相互作用而被激活。激活的中性粒细胞附着并穿过内皮细胞，并在血管壁内积聚。这些中性粒细胞脱颗粒并产生活性氧自由基，最终死亡，导致组织损伤。内皮损伤导致血清蛋白和凝血因子漏出，引起纤维蛋白样坏死。B 细胞产生 ANCAs，以及中性粒细胞异常和不同 T 细胞亚型的失衡，Th17 细胞过度增加，从而使炎症过程持续存在。
