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Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome
发布于：2013年8月19日 文字：【大】【中】【小】
Am J Transplant. 2013 Mar;13(3):663-75. doi: 10.1111/ajt.12077. Epub 2013 Jan 28.
Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome.
Le Quintrec M, Zuber J, Moulin B, Kamar N, Jablonski M, Lionet A, Chatelet V, Mousson C, Mourad G, Bridoux F, Cassuto E, Loirat C, Rondeau E, Delahousse M, Frémeaux-Bacchi V.
Source
Néphrologie et Transplantation Rénale, H?pital Foch, Suresnes, France. m.lequintrec@hopital-foch.org
Abstract
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 but not calcineurin inhibitor immunosuppressive treatment. 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.
© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.
不典型溶血尿毒综合征(aHUS)是一种严重的与补体旁路蛋白基因缺陷相关的疾病。目前只有少数的数据提示基因的缺陷与aHUS患者进行肾移植后复发的危险性以及移植器官的预后情况。这个研究的目的在于阐明肾移植后复发的危险性以及移植器官的预后的危险因素，重点在于补体蛋白的遗传背景。我们回顾性的分析了57例aHUS患者（共进行了71次肾移植）。其中有39例（68%）患者存在补体的基因突变，包括H因子(CFH), I因子 (CFI), 膜辅助蛋白(MCP), C3以及B 因子(CFB)。随访5年时，移植器官的存活率为51%（不包括患者死亡的情况）。疾病复发与移植肾脏失功相关(p = 0.001)。补体基因突变与高复发率相关(p = 0.009)。 出现H因子基因缺陷或者功能获得性突变（C3，CFB）的患者，具有较高的疾病复发率。M-TOR抑制剂与疾病复发高度相关(p = 0.043)，但与钙调磷酸酶抑制剂治疗不相关(p = 0.29)。血浆疗法的优先使用可以减少复发率(p = 0.07)。我们的研究指出补体基因异常可以预测复发相关的器官失功，并为个性化遗传学治疗提供了依据。