Department of Medicine, University of Colorado School of Medicine, Aurora, CO.
Adv Chronic Kidney Dis. 2020 Mar;27(2):86-94. doi: 10.1053/j.ackd.2019.10.003.
The complement cascade was first recognized as a downstream effector system of antibody-mediated cytotoxicity. Consistent with this view, it was discovered in the 1960s that complement is activated in the glomeruli of patients with immune complex glomerulonephritis. More recently, research has shown that complement system has many additional functions relating to regulation of the immune response, homeostasis, and metabolism. It has also become clear that the complement system is important to the pathogenesis of many non-immune complex mediated kidney diseases. In fact, in atypical hemolytic uremic syndrome and C3 glomerulopathy, uncontrolled complement activation is the primary driver of disease. Complement activation generates multiple pro-inflammatory fragments, and if not properly controlled it can cause fulminant tissue injury. Furthermore, the mechanisms of complement activation and complement-mediated injury vary from disease to disease. Many new drugs that target the complement cascade are in clinical development, so it is important to fully understand the biology of the complement system and its role in disease.
补体级联反应最初被认为是抗体介导的细胞毒性的下游效应系统。与此观点一致，人们在 20 世纪 60 年代发现，补体在免疫复合物性肾小球肾炎患者的肾小球中被激活。最近的研究表明，补体系统具有许多与调节免疫反应、内稳态和代谢相关的其他功能。现在也很清楚，补体系统对许多非免疫复合物介导的肾脏疾病的发病机制很重要。事实上，在非典型溶血性尿毒症综合征和 C3 肾小球病中，不受控制的补体激活是疾病的主要驱动因素。补体激活会产生多种促炎片段，如果不能得到适当控制，可能会导致暴发性组织损伤。此外，补体激活和补体介导的损伤的机制因疾病而异。许多针对补体级联反应的新药正在临床开发中，因此，充分了解补体系统的生物学及其在疾病中的作用非常重要。
