Complement mutation-associated de novo thrombotic microangiopathy following kidney transplantation
Complement mutation-associated de novo thrombotic microangiopathy following kidney transplantation
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DOI：
10.1111/j.1600-6143.2008.02297.x
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发表时间：
2008-08-01
影响因子：
8.8
通讯作者：
Fremeaux-Bacchi, V.
中科院分区：
文献类型：
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作者：
Le Quintrec, M.;Lionet, A.;Fremeaux-Bacchi, V.
一个或多个编码补体调节蛋白的基因突变容易导致非典型溶血性尿毒症综合征(AHUS)及其在肾移植后的复发。我们对24例发生新发血栓性微血管病(TMA)的肾移植受者进行了血浆补体水平的检测和补体因子H、I(CFH、CFI)及膜辅因子蛋白(MCP)基因突变的筛查。6例患者出现低C3和/或低B因子水平提示补体替代途径。24例患者中有7例(29%)发现CFH或CH基因突变，其中2例同时发生突变。相反，在没有TMA的对照肾移植患者组(n=25)中没有发现突变。有或没有突变的患者在临床特征上是相似的。24例患者中有8例在移植后1年内失去移植物，包括6例CFH突变或C3或CFB下降的患者。总之，患有新生TMA的肾移植患者表现出出人意料的高CFH和CFI突变频率。这些结果表明，基因异常可能是肾移植后新发TMA的危险因素，并提出了最佳治疗策略的问题。
Mutations in one or more genes encoding complement-regulatory proteins predispose to atypical hemolytic uremic syndrome (aHUS) and its recurrence following kidney transplantation. We evaluated plasma complement level and performed a screening for mutations in genes encoding complement Factors H and I (CFH, CFI) and membrane cofactor protein (MCP) in 24 kidney transplant recipients experiencing de novo thrombotic microangiopathy (TMA). Six patients presented with low C3 and/or low Factor B levels suggestive complement alternative pathway. A mutation in the CFH or CH gene was found in 7/24 patients (29%), two of whom had a mutation in both genes. On the contrary, no mutation was identified in a control kidney transplant patients group (n = 25) without TMA. Patients with or without mutations were similar with regard to clinical features. Eight out of 24 patients lost their graft within 1 year of posttransplantation including six patients with a CFH mutation or a decrease of C3 or CFB in plasma. To conclude, kidney transplant patients with de novo TMA exhibit an unexpectedly high frequency of CFH and CFI mutations. These results suggest that genetic abnormalities may represent risk factors for de novo TMA after kidney transplantation and raise the question of the best therapeutic strategy.