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

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 (P<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 (P<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) (P<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 (P>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, P=0.067; OR: 0.404, 95% CI: 0.000-2.625, P=0.172, respectively].

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

Keywords: acute rejection; human leukocyte antigen; liver transplantation; mismatch; next-generation sequencing.

Figure 1

Flow diagram of the study.

Figure 2

Comparison of overall survival (OS) between the AR and non-AR groups.

Figure 3

Risk of AR in liver transplant patients, according to donor-recipient mismatch between various combinations of 11 HLA loci. Class II includes HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1. The 11 loci include HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1.