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在以非裔美国人为主的肾移植队列中,使用HLAMatchmaker进行人类白细胞抗原表位匹配对移植结果的预测价值。

Predictive value of human leucocyte antigen epitope matching using HLAMatchmaker for graft outcomes in a predominantly African-American renal transplant cohort.

作者信息

Haririan Abdolreza, Fagoaga Omar, Daneshvar Hamidreza, Morawski Katherina, Sillix Dale H, El-Amm Jose M, West Miguel S, Garnick James, Migdal Stephen D, Gruber Scott A, Nehlsen-Cannarella Sandra

机构信息

Division of Nephrology, Department of Medicine, Wayne State University School of Medicine, Detroit, MI, USA.

出版信息

Clin Transplant. 2006 Mar-Apr;20(2):226-33. doi: 10.1111/j.1399-0012.2005.00473.x.

Abstract

The HLAMatchmaker program is based on the donor/recipient comparison of the polymorphic triplet amino-acid sequences of the antibody-accessible regions on the human leucocyte antigen (HLA) molecule. The previous reports on its predictive value for renal allograft outcomes are conflicting. We conducted a retrospective study in a predominantly African-American (AA) cohort (N = 101, 94% AA). HLA typing was performed by molecular methods and triplet matching using HLAMatchmaker. Study end points included graft survival and incidence of acute rejection. The relationship between the number of triplet mismatches (TMM) and the degree of HLA antigen MM was evaluated using Pearson's correlation coefficient. Logistic regression models were used to examine the association between triplet matching and the study end points. Kaplan-Meier and Cox proportional hazard models were used for graft survival analysis. The strongest relationship between the number of TMM and HLA antigen MM was observed for HLA-DQ (r = 0.88). The association between triplet matching at HLA-A, -B, -DR and -DRw HLA loci and the study end points was not statistically significant. However, after grouping, the unadjusted estimates of graft survival for those with more than 10 Class I TMM were significantly worse than the others (p = 0.03). Adjusting for the effect of donor source, recipient characteristics and the immunosuppressive regimen did not change this association (hazard ratio = 0.2, confidence interval = 0.04-1.1). We conclude that triplet matching using HLAMatchmaker can provide useful prognostic information in kidney transplantation and that more than 10 donor/recipient Class I HLA TMM is predictive of worse graft outcome.

摘要

HLAMatchmaker程序基于供体/受体对人类白细胞抗原(HLA)分子上抗体可及区域的多态性三联体氨基酸序列进行比较。先前关于其对肾移植结果预测价值的报告相互矛盾。我们在一个主要为非裔美国人(AA)的队列(N = 101,94%为AA)中进行了一项回顾性研究。采用分子方法进行HLA分型,并使用HLAMatchmaker进行三联体匹配。研究终点包括移植物存活和急性排斥反应的发生率。使用Pearson相关系数评估三联体错配数(TMM)与HLA抗原错配程度之间的关系。使用逻辑回归模型检验三联体匹配与研究终点之间的关联。采用Kaplan-Meier法和Cox比例风险模型进行移植物存活分析。观察到HLA-DQ的TMM数与HLA抗原错配之间的相关性最强(r = 0.88)。HLA-A、-B、-DR和-DRw HLA位点的三联体匹配与研究终点之间的关联无统计学意义。然而,分组后,I类TMM超过10个的患者移植物存活的未调整估计值明显低于其他患者(p = 0.03)。调整供体来源、受体特征和免疫抑制方案的影响后,这种关联没有改变(风险比 = 0.2,置信区间 = 0.04 - 1.1)。我们得出结论,使用HLAMatchmaker进行三联体匹配可为肾移植提供有用的预后信息,并且供体/受体I类HLA TMM超过10个可预测移植物预后较差。

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