Complement Genes Strongly Predict Recurrence and Graft Outcome in Adult Renal Transplant Recipients with Atypical Hemolytic and Uremic Syndrome
Complement Genes Strongly Predict Recurrence and Graft Outcome in Adult Renal Transplant Recipients with Atypical Hemolytic and Uremic Syndrome
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DOI：
10.1111/ajt.12077
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发表时间：
2013-03-01
影响因子：
8.8
通讯作者：
Fremeaux-Bacchi, V.
中科院分区：
文献类型：
--
作者：
Le Quintrec, M.;Zuber, J.;Fremeaux-Bacchi, V.
非典型溶血性尿毒症综合征（aHUS）是一种与补体替代途径的遗传异常密切相关的严重疾病。在肾移植后，根据aHUS患者的遗传背景，很少有关于复发风险和移植结果的数据。本研究的目的是确定复发和移植结果的危险因素，特别是补体基因异常的作用。我们回顾性研究了57例接受71例肾移植的aHUS患者。39例（68%）补体基因突变，分别为因子H （CFH）、因子I （CFI）、膜辅助因子蛋白（MCP）、C3和因子B （CFB）。5年后，经死亡审查的移植存活率为51%。疾病复发与移植物丢失相关（p = 0.001）。补体基因突变与较高的复发风险相关（p = 0.009）。CFH或功能获得（C3， CFB）突变的患者复发风险最高。M-TOR抑制剂与复发风险显著相关（p = 0.043），而钙调磷酸酶抑制剂免疫抑制治疗与复发风险无关（p = 0.29）。先发制人的血浆治疗有降低复发率的趋势（p = 0.07）。我们的研究强调，补体遗传异常的特征预测复发相关移植物丢失的风险，并为未来基于遗传的个体化预防治疗策略铺平了道路。
Atypical hemolytic and uremic syndrome (aHUS) is a severe disease strongly associated with genetic abnormalities in the complement alternative pathway. In renal posttransplantation, few data are available on recurrence risk and graft outcome according to genetic background in aHUS patients. The aim of this study was to identify risk factors for recurrence and transplant outcome and, in particular, the role of complement gene abnormalities. We retrospectively studied 57 aHUS patients who had received 71 renal transplants. A mutation in complement gene was identified in 39 (68%), in factor H (CFH), factor I (CFI), membrane cofactor-protein (MCP), C3 and factor B (CFB). At 5 years, death-censored graft survival was 51%. Disease recurrence was associated with graft loss (p = 0.001). Mutations in complement genes were associated with higher risk of recurrence (p = 0.009). Patients with CFH or gain of function (C3, CFB) mutations had a highest risk of recurrence. M-TOR inhibitor was associated with significant risk of recurrence (p = 0.043) but not calcineurin inhibitor immunosuppressive treatment (p = 0.29). Preemptive plasmatherapy was associated with a trend to decrease recurrence (p = 0.07). Our study highlights that characterization of complement genetic abnormalities predicts the risk of recurrence-related graft loss and paves the way for future genetically based individualized prophylactic therapeutic strategies.