Nephrology Unit, Meyer Children's Hospital, Firenze, Italy.
Department of Biomedical Experimental and Clinical Sciences 'Mario Serio', University of Firenze, Firenze, Italy.
Clin Exp Immunol. 2020 Dec;202(3):403-406. doi: 10.1111/cei.13515. Epub 2020 Oct 5.
The complement system plays a central role in autoimmune diseases, including anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Although complement deposition is scarce in AAV pathological samples, complement activation is required for the development of necrotizing crescentic glomerulonephritis (NCGN) in mouse models of AAV and occurs via the alternative pathway. The anaphylatoxin C5a, produced by the final complement pathway, is determinant to drive the disease in animal models. C5a primes human neutrophils and enhances their activation induced by ANCA; activated neutrophils, in turn, release factors that lead to C5a generation, establishing a self-amplifying loop. C5a is also significantly increased in the serum of AAV patients with active disease compared to those in remission or healthy controls. Inhibition of the C5a receptor with avacopan is an emerging therapy that will probably allow AAV treatment with glucocorticoid-free regimens.
补体系统在自身免疫性疾病中起着核心作用，包括抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）。尽管补体在 AAV 病理样本中的沉积很少，但补体的激活是导致 AAV 小鼠模型中坏死性新月体肾小球肾炎（NCGN）发生所必需的，并且是通过替代途径发生的。最终补体途径产生的过敏毒素 C5a 对于驱动动物模型中的疾病是决定性的。C5a 可激活人中性粒细胞并增强其由 ANCA 诱导的激活；活化的中性粒细胞反过来又会释放导致 C5a 生成的因子，从而建立自我放大循环。与缓解期或健康对照组相比，活动期 AAV 患者的血清中 C5a 明显增加。用 avacopan 抑制 C5a 受体是一种新兴的治疗方法，可能会允许 AAV 治疗无糖皮质激素方案。
