Background: Limited availability of allele-level HLA genotypes prompts their imputation from allele-group genotypes to estimate epitope mismatches. We evaluated the accuracy of epitope load and repertoire assignment when imputing allele-level HLA genotypes.
Methods: Analyses were conducted on 175 hematopoietic stem cell (HSC) donors from the Héma-Québec registry (HQR) and 57 HSC donor-recipient pairs from McGill University Health Centre (MUHC), Québec, Canada, genotyped for HLA-A, -B, -C, -DRB1 and -DQB1. Multi-locus allele-level imputation was performed using HaploStats. Disagreement in B- and T-cell epitope assignment and epitope mismatches were ascertained for imputed vs. measured allele-level HLA genotypes in HSC donors and donor-recipient pairs, respectively.
Results: Imputation resulted in no differences in overall eplet mismatches and PIRCHE-II for HLA-A, -B, and -C in 83.4% and 93.7% of HQR donors and 87.7% and 87.7% of MUHC donors, respectively. HLA-DRB1- and -DQB1-derived eplet mismatches and PIRCHE-II were correctly assigned in 72.0% and 85.1% of HQR donors and 70.2% and 71.9% of MUHC donors, respectively. No discrepancies in eplet load or PIRCHE-II were observed in 96.5% and 86.0% of HSC donor-recipient pairs and in 70.2% and 70.1% of pairs for HLA-A, -B and -C and -DRB1 and -DQB1, respectively. Kappa statistics of 0.9708 and 0.9725, 0.8724 and 0.8177, 0.9827 and 0.9022, 0.5644 and 0.4939, 0.5085 and 0.6361 were demonstrated when assessing agreement between eplet mismatches and PIRCHE-II of imputed vs. measured HLA-A, -B, -C, -DRB1 and -DQB1 types, respectively.
Conclusions: To avoid inaccuracies in epitope compatibility estimation, mainly for class II HLA, multi-locus allele-level genotype measurement is recommended. This article is protected by copyright. All rights reserved.
Keywords: Epitope; Eplet; HLAMatchmaker; HaploStats; Histocompatibility; PIRCHE.
This article is protected by copyright. All rights reserved.