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Updated: Mar 10, 2026
Personalized Peptide Arrays for Detection of HLA Alloantibodies in Organ Transplantation
Published on: September 6, 2017
Human Leukocyte Antigen Alleles and Oral Microbiome Association With Antibody-mediated Rejection in Living-donor
Manjeet Kaur1, Rosmy Babu1, Sukriti Baweja2
1Departments of Pathology, Institute of Liver and Biliary Sciences, D1, Vasant Kunj, New Delhi, India.
Background/Aims:
Antibody-mediated rejection (ABMR) is an important cause of graft dysfunction after liver transplantation, yet the combined influence of human leukocyte antigen (HLA) immunogenetics and the oral microbiome on ABMR risk is not well defined.
Methods:
In this prospective cohort of 180 living donor-recipient pairs, pre-transplant 16S ribosomal ribonucleic acid sequences and high-resolution HLA genotyping were done. The human leukocyte antigen epitope mismatch algorithm quantified amino acid and solvent-accessible mismatches. Oral microbiome profiles were generated using the Divisive Amplicon Denoising Algorithm (DADA2) and quantitative insights into microbial ecology version 2 (QIIME2). Associations between HLA alleles and microbial taxa were assessed using generalized linear models and linear discriminant analysis effect size (LEfSe). ABMR was diagnosed as per Banff criteria over one year.
Results:
ABMR was diagnosed in 15 patients. These patients had significantly higher mismatch burdens at HLA-DPB1, DQB1, and DRB1 than non-ABMR recipients. Across the cohort, 68 HLA alleles demonstrated distinct microbial associations at phylum, family, and genus levels. Alleles such as HLA-DRB108, HLA-DPB1575, and HLA-C05 were linked to differential abundance of Actinobacteriota, Campylobacterota, and Fusobacteriota, respectively. Genus-level analyses revealed strong allele-specific associations with Veillonella, Enterobacter, Streptococcus, and other immunomodulatory taxa. LEfSe identified HLA-DQB106 and HLA-DQB1∗104 as associated with enrichment of Enterobacter, Citrobacter europaeus, Bacteroides plebeius, Rothia dentocariosa, Megasphaera, and Burkholderiaceae-microbial signatures also prominent in ABMR cases.
Conclusion:
Class II HLA mismatch burden and allele-specific oral microbial signatures are closely linked to ABMR. Combined HLA-microbiome profiling may enhance early risk stratification and inform targeted peri-transplant microbial interventions.
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