Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, AA53, Postbus 196, 9700 AD, Groningen, the Netherlands.
Division of Nephrology and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Mol Immunol. 2020 Dec;128:175-187. doi: 10.1016/j.molimm.2020.10.015. Epub 2020 Nov 1.
It has long been known that the complement cascade is activated in various forms of glomerulonephritis. In many of these diseases, immune-complexes deposit in the glomeruli and activate the classical pathway. Researchers have also identified additional mechanisms by which complement is activated in the kidney, including diseases in which the alternative and lectin pathways are activated. The kidney appears to be particularly susceptible to activation of the alternative pathway, and this pathway has been implicated as a primary driver of atypical hemolytic uremic syndrome, C3 glomerulopathy, anti-neutrophil cytoplasmic antibody-associated vasculitis, as well as some forms of immune-complex glomerulonephritis. In this paper we review the shared and distinct mechanisms by which complement is activated in these different diseases. We also review the opportunities for using therapeutic complement inhibitors to treat kidney diseases.
长期以来，人们已经知道补体级联反应在各种形式的肾小球肾炎中被激活。在这些疾病中，免疫复合物沉积在肾小球中并激活经典途径。研究人员还发现了补体在肾脏中被激活的其他机制，包括替代途径和凝集素途径被激活的疾病。肾脏似乎特别容易被替代途径激活，该途径被认为是非典型溶血性尿毒症综合征、C3 肾小球病、抗中性粒细胞胞质抗体相关性血管炎以及某些形式的免疫复合物性肾小球肾炎的主要驱动因素。本文综述了补体在这些不同疾病中被激活的共同和独特机制。我们还回顾了使用治疗性补体抑制剂治疗肾脏疾病的机会。
