Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome
Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome
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DOI：
10.1681/asn.2006080811
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发表时间：
2007-08-01
影响因子：
13.6
通讯作者：
Loirat, Chantal
中科院分区：
文献类型：
--
作者：
Sellier-Leclerc, Anne-Laure;Fremeaux-Bacchi, Veronique;Loirat, Chantal
因子H（CFH）、因子I（IF）和膜辅因子蛋白（MCP）基因突变已被描述为非典型溶血性尿毒综合征（阿胡斯）的危险因素。本研究分析了补体突变对46例阿胡斯患儿结局的影响。共有52%的患者在一个或两个已知的易感因素中发生突变（分别有22%、13%和15%的患者发生CFH、IF或MCP突变; 2%的患者发生CFH+ IF突变）。发病时年龄< 3个月似乎是CFH和IF突变相关allUS的特征。CFH突变组预后最差，60%的患者在1年内达到终末期肾病或死亡。只有30%的CFH突变位于SCR 20中。MCP突变相关的HUS有复发过程，但没有儿童在1岁时达到ESIRD。有一半的IF突变的患者迅速演变为ESRD，一半恢复。血浆疗法似乎对除MCP突变组外的所有组中三分之一的患者有有益效果。在15例患者中进行的24例肾移植中，只有8例（33%）成功。移植物失败是由于早期移植物血栓形成（50%）或HUS复发。总之，CFH突变患者的HUS结局是灾难性的，除MCP突变组外，所有组的移植后结局均较差。新的治疗方法是迫切需要的，进一步的研究应该阐明无法解释的HUS组。
Mutations in factor H (CFH), factor I (IF), and membrane cofactor protein (MCP) genes have been described as risk factors for atypical hemolytic uremic syndrome (aHUS). This study analyzed the impact of complement mutations on the outcome of 46 children with aHUS. A total of 52% of patients had mutations in one or two of known susceptibility factors (22, 13, and 15% of patients with CFH, IF, or MCP mutations, respectively; 2% with CFH+ IF mutations). Age < 3 mo at onset seems to be characteristic of CFH and IF mutation-associated allUS. The most severe prognosis was in the CFH mutation group, 60% of whom reached ESRD or died within < 1 yr. Only 30% of CFH mutations were localized in SCR20. MCP mutation-associated HUS has a relapsing course, but none of the children reached ESIRD at 1 yr. Half of patients with IF mutation had a rapid evolution to ESRD, and half recovered. Plasmatherapy seemed to have a beneficial effect in one third of patients from all groups except for the MCP mutation group. Only eight (33%) of 24 kidney transplantations that were performed in 15 patients were successful. Graft failures were due to early graft thrombosis (50%) or HUS recurrence. In conclusion, outcome of HUS in patients with CFH mutation is catastrophic, and posttransplantation outcome is poor in all groups except for the MCP mutation group. New therapies are urgently needed, and further research should elucidate the unexplained HUS group.