原发性小血管炎发病机制研究进展

Progress of research on pathogenesis of primary small vasculitis

抗中性粒细胞胞浆抗体(ANCA)相关小血管炎(AAV)是一类常见的自身免疫性疾病,肾脏是其最常受累的器官之一,进展迅速,预后凶险,ANCA是其特异性的血清学标志物。AAV的发病机制目前尚未完全阐明,但ANCA、中性粒细胞、补体三者的相互作用是其中的核心。中性粒细胞在补体C5a等炎症因子的作用下,其表面表达ANCA靶抗原水平增加,在ANCA的作用下,中性粒细胞发生呼吸爆发和脱颗粒,并形成中性粒细胞细胞外罗网,导致血管内皮细胞的损伤;中性粒细胞活化还可以进一步激活补体旁路途经,促使形成C3转化酶和C5转化酶,产生更多的补体活化产物C5a,从而进一步放大炎症效应,导致AAV的发生。此外,淋巴细胞和抗内皮细胞抗体在AAV的发病机制中也发挥了重要作用。

Antineutrophil cytoplasmic antibody （ANCA） associated vasculitis （AAV） is a group of common autoimmune diseases in which the kidney is one of the most involved organs with rapid progression and poor prognosis. ANCAs are specific serological markers of AAV. The pathogenesis of AAV has not yet been fully elucidated. However, the interaction among ANCA, neutrophil, and complement system plays a central role. Proinflamrnatory factors including C5a can prime neutrophils to express more target antigens for ANCA on neutrophil surface. ANCAs activate primed neutrophils to undergo a respiratory burst, degrannlation, and produce neutrophil extracellular traps （NETs） , which result in vascular endothelial cell injury. In addition, activation of neutrophil can activate complement alternative pathway to form C3 and C5 convertases and produce more C5a, thereby amplifying inflammation and leading to AAV. Besides, lymphocytes and anti-endothelial cell antibodies （AECA） also play an important role in pathogenesis of AAV.