Frémeaux-Bacchi Véronique
INSERM UMR_S1135, Centre de Recherche des Cordeliers, Équipe « Complément et Maladies », 15 rue de l'École de Médecine, 75006 Paris, France - Hôpital Européen Georges Pompidou, Laboratoire d'Immunologie, 20 rue Leblanc, 75015 Paris, France.
Biol Aujourdhui. 2013;207(4):231-40. doi: 10.1051/jbio/2013027. Epub 2014 Mar 5.
Hemolytic Uremic Syndrome (HUS) is characterized by the triad of hemolytic anemia, thrombocytopenia and acute renal failure. The most frequent form in children is caused by Shiga-toxin producing Escherichia coli. In absence of Shiga-toxin infection, the HUS is called atypical (aHUS). Some HUS are secondary to Streptococcus pneumonia or human immunodeficiency virus infection, cancer, anti-cancer drugs, or cyclosporine. During the last decade, aHUS has been demonstrated to be a disorder of complement alternative pathway regulation. aHUS must be regarded as a complex polygenic disease which results from a combination of genetic risk factors. Approximately 60% of patients have mutations in the genes encoding complement factor H (20-30% of patients), MCP (10-15%), factor I (4-10%), factor B (1-2%) or C3 (5-10%), and 6% have anti-factor H antibodies. Prognosis is severe whereas the clinical features vary according to complement abnormality. aHUS touches both children and adults, but in children very early onset is characteristic of factor H and factor I-HUS, while MCP-HUS is not observed before the age of 1. Half of patients with adult onset have a rapid evolution to end-stage renal disease, but half recover. The best prognosis is in patients with MCP (Membrane Cofactor Protein) mutation and a pediatric onset of the disease, who have a relapsing course, but a risk of end-stage renal disease of only 15-30% at 5 years follow-up. Anti-factor H antibodies-HUS is mainly observed in (pre)adolescents and appears to have a favourable outcome if treated early. There is a high risk of post-transplant recurrence in all groups, except MCP-HUS. These findings have paved the way for innovative therapeutic strategies based on complement blockade, and eculizumab, a monoclonal antibody targeting the human complement component 5, is now widely used to treat aHUS. Mutations in the gene of thrombomodulin and diacylglycerol kinase epsilon (DGKe) have been reported, suggesting the possibility of an alternative or more complex disease-causing mechanism than previously thought.
溶血尿毒综合征（HUS）的特征是溶血性贫血、血小板减少和急性肾衰竭三联征。儿童中最常见的类型是由产志贺毒素的大肠杆菌引起的。在没有志贺毒素感染的情况下，HUS被称为非典型（aHUS）。一些HUS继发于肺炎链球菌或人类免疫缺陷病毒感染、癌症、抗癌药物或环孢素。在过去十年中，已证明aHUS是补体替代途径调节紊乱。aHUS必须被视为一种复杂的多基因疾病，它是由遗传风险因素共同作用导致的。大约60%的患者在编码补体因子H（20 - 30%的患者）、膜辅蛋白（MCP，10 - 15%）、因子I（4 - 10%）、因子B（1 - 2%）或C3（5 - 10%）的基因中存在突变，6%的患者有抗因子H抗体。预后严重，而临床特征根据补体异常情况而有所不同。aHUS在儿童和成人中均可发生，但在儿童中，极早期发病是因子H和因子I - HUS的特征，而MCP - HUS在1岁之前不会出现。成人发病的患者中有一半会迅速发展为终末期肾病，但另一半会康复。预后最好的是患有MCP（膜辅蛋白）突变且疾病在儿童期发病的患者，他们病程呈复发型，但在5年随访时终末期肾病的风险仅为15 - 30%。抗因子H抗体 - HUS主要见于（青春期）前青少年，若早期治疗似乎预后良好。除MCP - HUS外，所有组移植后复发风险都很高。这些发现为基于补体阻断的创新治疗策略铺平了道路，目前一种靶向人类补体成分5的单克隆抗体依库珠单抗已被广泛用于治疗aHUS。已报道血栓调节蛋白和二酰甘油激酶ε（DGKe）基因的突变，这表明可能存在比以前认为的更复杂的致病机制。
