Liszewski M Kathryn, Java Anuja, Schramm Elizabeth C, Atkinson John P
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110; email:
Division of Nephrology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Annu Rev Pathol. 2017 Jan 24;12:25-52. doi: 10.1146/annurev-pathol-012615-044145. Epub 2016 Dec 5.
The vertebrate complement system consists of sequentially interacting proteins that provide for a rapid and powerful host defense. Nearly 60 proteins comprise three activation pathways (classical, alternative, and lectin) and a terminal cytolytic pathway common to all. Attesting to its potency, nearly half of the system's components are engaged in its regulation. An emerging theme over the past decade is that variations in these inhibitors predispose to two scourges of modern humans. One, occurring most often in childhood, is a rare but deadly thrombomicroangiopathy called atypical hemolytic uremic syndrome. The other, age-related macular degeneration, is the most common form of blindness in the elderly. Their seemingly unrelated clinical presentations and pathologies share the common theme of overactivity of the complement system's alternative pathway. This review summarizes insights gained from contemporary genetics for understanding how dysregulation of this powerful innate immune system leads to these human diseases.
脊椎动物补体系统由一系列相互作用的蛋白质组成，这些蛋白质为宿主提供快速而强大的防御。近60种蛋白质构成了三条激活途径（经典途径、替代途径和凝集素途径）以及一条所有途径共有的末端溶细胞途径。该系统的效力可见一斑，其近一半的组分都参与了调节过程。在过去十年中出现的一个共同主题是，这些抑制剂的变异会使人易患现代人类的两大灾祸。一种灾祸最常发生在儿童期，是一种罕见但致命的血栓性微血管病，称为非典型溶血尿毒综合征。另一种是与年龄相关的黄斑变性，是老年人中最常见的失明形式。它们看似不相关的临床表现和病理有一个共同主题，即补体系统替代途径的过度激活。本综述总结了当代遗传学所获得的见解，以了解这个强大的先天免疫系统的失调如何导致这些人类疾病。
