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肺移植受者中的HLA-E(⁎)01:03等位基因与较高的慢性肺移植功能障碍发生率相关。

HLA-E(⁎)01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence.

作者信息

Di Cristofaro Julie, Pelardy Mathieu, Loundou Anderson, Basire Agnès, Gomez Carine, Chiaroni Jacques, Thomas Pascal, Reynaud-Gaubert Martine, Picard Christophe

机构信息

CNRS, EFS, ADES UMR 7268, Aix-Marseille Université, 13916 Marseille, France.

Immunogenetics Laboratory, EFS-Alpes Méditerranée, 13005 Marseille, France.

出版信息

J Immunol Res. 2016;2016:1910852. doi: 10.1155/2016/1910852. Epub 2016 Jul 17.

Abstract

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E(⁎)01:01 and HLA-E(⁎)01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, HLA-E(⁎)01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E(⁎)01:01 status (HR: 3.563 (CI 95%, 1.016-12), p = 0.047). HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.

摘要

肺移植(LTx)是终末期肺病特定患者的有效治疗选择。例如,在造血干细胞移植中,HLA-E似乎在对不同病毒感染的免疫反应中起主要作用,并影响移植结果。两个非同义等位基因HLA-E(⁎)01:01和HLA-E(⁎)01:03存在功能差异,涉及相对肽亲和力、细胞表面表达以及自然杀伤细胞的潜在裂解活性。这项回顾性研究的目的是确定这两个等位基因对肺移植受者的抗HLA同种免疫风险、总生存率和慢性排斥反应(CLAD)的影响。对1998年至2010年在单个移植中心接受肺移植的119名受者进行了HLA-E基因分型。在单变量分析中,与杂合HLA-E等位基因相比,两种HLA-E纯合状态均与总生存率受损相关(p = 0.01)。在多变量分析中,与HLA-E(⁎)01:01纯合状态相比,HLA-E(⁎)01:03等位基因显示CLAD发生率增加(风险比:3.563(95%置信区间,1.016 - 12),p = 0.047)。HLA-E等位基因不影响病原体感染或新生供者特异性抗体(DSA)的产生。这项回顾性研究显示了HLA-E等位基因与肺移植之间未被研究的有害关联,需要使用更大的队列进行验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e2e/4967441/cfe90b84f900/JIR2016-1910852.001.jpg

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