Jokiranta T Sakari
Research Programs Unit, Immunobiology, University of Helsinki, Helsinki University Central Hospital, and United Medix Laboratories, Helsinki, Finland
Blood. 2017 May 25;129(21):2847-2856. doi: 10.1182/blood-2016-11-709865. Epub 2017 Apr 17.
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis, thrombocytopenia, and acute kidney failure. HUS is usually categorized as typical, caused by Shiga toxin-producing (STEC) infection, as atypical HUS (aHUS), usually caused by uncontrolled complement activation, or as secondary HUS with a coexisting disease. In recent years, a general understanding of the pathogenetic mechanisms driving HUS has increased. Typical HUS (ie, STEC-HUS) follows a gastrointestinal infection with STEC, whereas aHUS is associated primarily with mutations or autoantibodies leading to dysregulated complement activation. Among the 30% to 50% of patients with HUS who have no detectable complement defect, some have either impaired diacylglycerol kinase ε (DGKε) activity, cobalamin C deficiency, or plasminogen deficiency. Some have secondary HUS with a coexisting disease or trigger such as autoimmunity, transplantation, cancer, infection, certain cytotoxic drugs, or pregnancy. The common pathogenetic features in STEC-HUS, aHUS, and secondary HUS are simultaneous damage to endothelial cells, intravascular hemolysis, and activation of platelets leading to a procoagulative state, formation of microthrombi, and tissue damage. In this review, the differences and similarities in the pathogenesis of STEC-HUS, aHUS, and secondary HUS are discussed. Common for the pathogenesis seems to be the vicious cycle of complement activation, endothelial cell damage, platelet activation, and thrombosis. This process can be stopped by therapeutic complement inhibition in most patients with aHUS, but usually not those with a DGKε mutation, and some patients with STEC-HUS or secondary HUS. Therefore, understanding the pathogenesis of the different forms of HUS may prove helpful in clinical practice.
溶血性尿毒症综合征（HUS）是一种血栓性微血管病，其特征为血管内溶血、血小板减少和急性肾衰竭。HUS通常分为典型型，由产志贺毒素大肠杆菌（STEC）感染引起；非典型HUS（aHUS），通常由补体激活失控所致；或继发性HUS，伴有共存疾病。近年来，对导致HUS的发病机制有了更全面的认识。典型HUS（即STEC-HUS）继发于STEC引起的胃肠道感染，而aHUS主要与导致补体激活失调的突变或自身抗体有关。在30%至50%未检测到补体缺陷的HUS患者中，一些患者存在二酰基甘油激酶ε（DGKε）活性受损、钴胺素C缺乏或纤溶酶原缺乏。一些患者患有继发性HUS，伴有共存疾病或触发因素，如自身免疫、移植、癌症、感染、某些细胞毒性药物或妊娠。STEC-HUS、aHUS和继发性HUS的共同发病特征是内皮细胞同时受损、血管内溶血以及血小板激活，导致促凝状态、微血栓形成和组织损伤。在本综述中，将讨论STEC-HUS、aHUS和继发性HUS发病机制的差异和相似之处。发病机制的共同点似乎是补体激活、内皮细胞损伤、血小板激活和血栓形成的恶性循环。在大多数aHUS患者中，这一过程可通过治疗性补体抑制来阻断，但DGKε突变患者以及一些STEC-HUS或继发性HUS患者通常无法阻断。因此，了解不同形式HUS的发病机制在临床实践中可能会有所帮助。
