Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases, Aldo e Cele Daccò, Via Camozzi, 3-24020 Ranica (BG), Italy.
Clin J Am Soc Nephrol. 2010 Oct;5(10):1844-59. doi: 10.2215/CJN.02210310. Epub 2010 Jul 1.
Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Most childhood cases are caused by Shiga toxin-producing bacteria. The other form, atypical HUS (aHUS), accounts for 10% of cases and has a poor prognosis. Genetic complement abnormalities have been found in aHUS.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We screened 273 consecutive patients with aHUS for complement abnormalities and studied their role in predicting clinical phenotype and response to treatment. We compared mutation frequencies and localization and clinical outcome in familial (82) and sporadic (191) cases.
In >70% of sporadic and familial cases, gene mutations, disease-associated factor H (CFH) polymorphisms, or anti-CFH autoantibodies were found. Either mutations or CFH polymorphisms were also found in the majority of patients with secondary aHUS, suggesting a genetic predisposition. Familial cases showed a higher prevalence of mutations in SCR20 of CFH and more severe disease than sporadic cases. Patients with CFH or THBD (thrombomodulin) mutations had the earliest onset and highest mortality. Membrane-cofactor protein (MCP) mutations were associated with the best prognosis. Plasma therapy induced remission in 55 to 80% of episodes in patients with CFH, C3, or THBD mutations or autoantibodies, whereas patients with CFI (factor I) mutations were poor responders. aHUS recurred frequently after kidney transplantation except for patients with MCP mutations.
Results underline the need of genetic screening for all susceptibility factors as part of clinical management of aHUS and for identification of patients who could safely benefit from kidney transplant.
溶血尿毒综合征（HUS）的特征为微血管性溶血性贫血、血小板减少和肾功能损害。大多数儿童病例由产志贺毒素的细菌引起。另一种形式，非典型 HUS（aHUS）占病例的 10%，预后较差。aHUS 中发现了遗传补体异常。
设计、环境、参与者和测量方法：我们筛选了 273 例连续的 aHUS 患者的补体异常，并研究了它们在预测临床表型和治疗反应中的作用。我们比较了家族性（82 例）和散发性（191 例）病例中的突变频率和定位以及临床结局。
在>70%的散发性和家族性病例中，发现了基因突变、疾病相关因子 H（CFH）多态性或抗 CFH 自身抗体。继发性 aHUS 的大多数患者也发现了突变或 CFH 多态性，提示存在遗传易感性。家族性病例中 CFH 的 SCR20 突变和更严重的疾病比散发性病例更常见。CFH 或 THBD（血栓调节蛋白）突变的患者发病最早，死亡率最高。膜辅因子蛋白（MCP）突变与最佳预后相关。在 CFH、C3 或 THBD 突变或自身抗体的患者中，血浆治疗诱导缓解的比例为 55%至 80%，而 CFI（因子 I）突变的患者反应不佳。除了 MCP 突变的患者外，aHUS 在肾移植后经常复发。
结果强调了需要对所有易感因素进行基因筛查，作为 aHUS 临床管理的一部分，并识别出可以安全受益于肾移植的患者。
