采用下一代测序技术研究供受者间人类白细胞抗原错配对肝移植急性排斥反应的影响：一项单中心研究

Impact of human leukocyte antigen mismatch between donor-recipient on acute rejection in liver transplantation using next-generation sequencing: a single-center study.

作者信息

Lu Genjie, Lu Yangfang, He Yanmin, Chen Wei, Zhu Faming

机构信息

Department of Blood Transfusion, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China.

Department of Radiotherapy, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China.

出版信息

Front Immunol. 2025 May 20;16:1576815. doi: 10.3389/fimmu.2025.1576815. eCollection 2025.

DOI:10.3389/fimmu.2025.1576815

PMID:40463387

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12129760/

Abstract

BACKGROUND

The effect of human leukocyte antigen (HLA) mismatch on acute rejection (AR) in liver transplantation (LT) is controversial. This study aimed to investigate the effect of donor-recipient mismatch at the HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1 loci on AR in LT.

METHODS

In total, 92 patients who underwent LT were selected for investigation from 1 January 2018 to 30 June 2024, and the donors of these patients were also from the same hospital. All donor and recipient specimens were genotyped via next-generation sequencing (NGS) for the 11 HLA loci. The patients were divided into AR and non-AR groups according to whether AR occurred after LT.

RESULTS

A total of 12 cases (13.04%) experienced AR after LT. The proportion of chronic hepatitis B virus (HBV) infection was lower in the AR group than that in the non-AR group (<0.05), while the proportion of split LT and mortality within 1 year after transplantation was higher in the AR group than in the non-AR group (<0.05). Compared with the non-AR group, the AR group had a significantly higher proportion of high-mismatch DQB1 (2 vs. 0-1) and DRB1+DQB1 (4 vs. 0-3) (<0.05) at the allele level, and other mismatches of a single locus and different combinations of the 11 HLA loci had no significant differences between the two groups (>0.05). However, neither high-mismatch DQB1 nor high-mismatch DRB1+DQB1 at the allele level was an independent risk factor for AR after adjustment for chronic HBV infection, LT operative procedures, and immunosuppressive regimen using bootstrapping [odds ratio (OR): 0.203, 95% confidence interval (CI): 0.000-1.300, =0.067; OR: 0.404, 95% CI: 0.000-2.625, =0.172, respectively].

CONCLUSION

In this preliminary study, no correlation between HLA mismatch at the allele level and post-transplant AR episodes was found.

摘要

背景

人类白细胞抗原（HLA）错配在肝移植（LT）中对急性排斥反应（AR）的影响存在争议。本研究旨在探讨供受者在HLA - A、- B、- C、- DRB1、- DRB3、- DRB4、- DRB5、- DQA1、- DQB1、- DPA1和 - DPB1位点的错配对肝移植中急性排斥反应的影响。

方法

选取2018年1月1日至2024年6月30日期间接受肝移植的92例患者进行调查，这些患者的供者也来自同一家医院。所有供者和受者标本均通过下一代测序（NGS）对11个HLA位点进行基因分型。根据肝移植后是否发生急性排斥反应，将患者分为急性排斥反应组和非急性排斥反应组。

结果

共有12例（13.04%）患者在肝移植后发生急性排斥反应。急性排斥反应组慢性乙型肝炎病毒（HBV）感染比例低于非急性排斥反应组（<0.05），而急性排斥反应组劈离式肝移植比例及移植后1年内死亡率高于非急性排斥反应组（<0.05）。与非急性排斥反应组相比，急性排斥反应组在等位基因水平上高错配的DQB1（2例 vs. 0 - 1例）和DRB1 + DQB1（4例 vs. 0 - 3例）比例显著更高（<0.05），而11个HLA位点的其他单一位点错配及不同组合在两组之间无显著差异（>0.05）。然而，在对慢性HBV感染、肝移植手术操作和免疫抑制方案进行自抽样调整后，等位基因水平上的高错配DQB1和高错配DRB1 + DQB1均不是急性排斥反应的独立危险因素[比值比（OR）：0.203，95%置信区间（CI）：0.000 - 1.300，P = 0.067；OR：0.404，95% CI：0.000 - 2.625，P = 0.172]。