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

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1576815

DOI=10.3389/fimmu.2025.1576815

ISSN=1664-3224

ABSTRACT=BackgroundThe 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.MethodsIn 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.ResultsA 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].ConclusionIn this preliminary study, no correlation between HLA mismatch at the allele level and post-transplant AR episodes was found.