Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, 308 Brinkhous-Bullitt Building, CB#7525, Chapel Hill, NC 27599-7525, USA.
Nat Rev Rheumatol. 2014 Aug;10(8):463-73. doi: 10.1038/nrrheum.2014.103. Epub 2014 Jul 8.
Antineutrophil cytoplasmic autoantibodies (ANCAs) are the probable cause of a distinct form of vasculitis that can be accompanied by necrotizing granulomatosis. Clinical and experimental evidence supports a pathogenesis that is driven by ANCA-induced activation of neutrophils and monocytes, producing destructive necrotizing vascular and extravascular inflammation. Pathogenic ANCAs can originate from precursor natural autoantibodies. Pathogenic transformation might be initiated by commensal or pathogenic microbes, legal or illegal drugs, exogenous or endogenous autoantigen complementary peptides, or dysregulated autoantigen expression. The ANCA autoimmune response is facilitated by insufficient T-cell and B-cell regulation. A putative pathogenic mechanism for vascular inflammation begins with ANCA-induced activation of primed neutrophils and monocytes leading to activation of the alternative complement pathway, which sets in motion an inflammatory amplification loop in the vessel wall that attracts and activates neutrophils with resultant respiratory burst, degranulation, extrusion of neutrophil extracellular traps, apoptosis and necrosis. The pathogenesis of extravascular granulomatosis is less clear, but a feasible scenario proposes that a prodromal infectious or allergic condition positions primed neutrophils in extravascular tissue in which they can be activated by ANCAs in interstitial fluid to produce extravascular necrotizing injury that would initiate an innate granulomatous inflammatory response to wall off the necrotic debris.
抗中性粒细胞胞浆抗体（ANCA）是一种独特血管炎形式的可能病因，这种血管炎可能伴有坏死性肉芽肿病。临床和实验证据支持一种发病机制，即由 ANCA 诱导的中性粒细胞和单核细胞激活驱动，导致破坏性坏死性血管和血管外炎症。致病性 ANCAs 可能源自前体天然自身抗体。致病性转化可能由共生体或病原体微生物、合法或非法药物、外源性或内源性自身抗原互补肽或自身抗原表达失调引发。ANCA 自身免疫反应受到 T 细胞和 B 细胞调节不足的促进。血管炎症的一个假设发病机制始于 ANCA 诱导的被激活的中性粒细胞和单核细胞的激活，导致替代补体途径的激活，从而在血管壁中引发炎症放大环，吸引并激活中性粒细胞，导致呼吸爆发、脱颗粒、中性粒细胞细胞外陷阱的挤出、凋亡和坏死。血管外肉芽肿病的发病机制尚不清楚，但一个可行的方案提出，前驱感染或过敏状态使被激活的中性粒细胞在血管外组织中定位，在间质液中，它们可以被 ANCAs 激活，导致血管外坏死性损伤，从而引发先天的肉芽肿性炎症反应，以隔离坏死的碎片。
