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对于已经产生新型供体特异性抗体的肾移植受者,HLA 有效等位基因错配程度是否为移植物丢失的危险因素?

Is the level of HLA eplet mismatch a risk factor for graft loss among kidney transplant recipients who have already formed de novo donor specific antibody?

机构信息

Jinling Hospital, Nanjing University School of Medicine, China.

Emory Transplant Center and Division of Nephrology and Hypertension, Emory University School of Medicine, Atlanta, GA, United States.

出版信息

Hum Immunol. 2021 Apr;82(4):240-246. doi: 10.1016/j.humimm.2021.02.004. Epub 2021 Feb 20.

DOI:10.1016/j.humimm.2021.02.004
PMID:33618904
Abstract

Eplet mismatches are associated with de novo DSA (dnDSA) and antibody mediated rejection (ABMR) among the general kidney transplant population. However, it is unclear whether the level of eplet mismatch can be used for risk stratification among patients with dnDSA. We performed a retrospective observational study of kidney transplant recipients with dnDSA (n = 44) transplanted between 10/2007 and 5/2014 to evaluate eplet mismatch as a risk factor for ABMR and allograft loss among dnDSA patients. High resolution typing was inferred from by imputation based on ethnicity and NMDP haplotypes, and the eplet mismatch was calculated using the Epvix algorithm. Biopsies (N = 151) from 95.3%(42/44) of patients were reviewed. The mean (SD) eplet mismatch was 69.8(22.8). The ABMR incidence was 71.4% (30/42) and 5 year death censored allograft survival was 67.4% during the mean (SD) follow-up of 5.3 (3.1) years. ABMR and death-censored allograft survival were not correlated with eplet mismatch among dnDSA patients. However, medication adherence and dnDSA MFI < 3000 were associated with reduced ABMR incidence. Among patients with both of these favorable characteristics, only 35.7% (15/42) developed ABMR. In conclusion, the level of eplet mismatch does not correlate with ABMR or allograft loss among high risk kidney transplant patients with dnDSA.

摘要

Eplet 错配与新诊断的 DSA(dnDSA)和抗体介导的排斥反应(ABMR)有关,在一般的肾移植人群中。然而,尚不清楚 Eplet 错配的水平是否可用于 dnDSA 患者的风险分层。我们对 2007 年 10 月至 2014 年 5 月间接受 dnDSA(n=44)肾移植的患者进行了一项回顾性观察性研究,以评估 Eplet 错配作为 dnDSA 患者 ABMR 和移植物丢失的危险因素。高分辨率分型是通过基于种族和 NMDP 单倍型的推断进行的,Eplet 错配是使用 Epvix 算法计算的。对 44 例患者中的 95.3%(42/44)进行了活检。患者的平均(SD)Eplet 错配为 69.8(22.8)。ABMR 发生率为 71.4%(30/42),在平均(SD)5.3(3.1)年的随访中,5 年死亡censored 移植物存活率为 67.4%。ABMR 和死亡 censored 移植物存活率与 dnDSA 患者的 Eplet 错配无关。然而,药物依从性和 dnDSA MFI<3000 与降低 ABMR 发生率有关。在具有这些有利特征的患者中,只有 35.7%(15/42)发生 ABMR。总之,在具有 dnDSA 的高风险肾移植患者中,Eplet 错配的水平与 ABMR 或移植物丢失无关。

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引用本文的文献

1
Combined Analysis of HLA Class II Eplet Mismatch and Tacrolimus Levels for the Prediction of De Novo Donor Specific Antibody Development in Kidney Transplant Recipients.联合分析 HLA Ⅱ类 Eplet 错配和他克莫司水平预测肾移植受者中新型供体特异性抗体的发展。
Int J Mol Sci. 2022 Jul 1;23(13):7357. doi: 10.3390/ijms23137357.
2
Pediatric Kidney Transplantation-Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching.小儿肾移植——我们能做得更好吗?表位/表位组匹配的前景与局限
Front Pediatr. 2022 Jun 3;10:893002. doi: 10.3389/fped.2022.893002. eCollection 2022.