Y D'Souza1, A Ferradji1, C Saw2, K Oualkacha3, L Richard4, G Popradi1,5, R Sapir-Pichhadze1,6,7,8. 1. Research Institute, McGill University Health Centre, Montréal, Québec, Canada. 2. Histocompatibility Laboratory, Division of Hematology, Department of Medicine, McGill University, Montréal, Québec, Canada. 3. Department of Mathematics, Université du Québec À Montréal, Montréal, Québec, Canada. 4. Héma-Québec, Saint-Laurent, Québec, Canada. 5. Division of Hematology, Department of Medicine, McGill University, Montréal, Québec, Canada. 6. Division of Nephrology, Department of Medicine, McGill University, Montréal, Québec, Canada. 7. Centre for Outcomes Research and Evaluation (CORE), McGill University Health Centre, Montréal, Québec, Canada. 8. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada.
Abstract
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. This article is protected by copyright. All rights reserved.
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. This article is protected by copyright. All rights reserved.
Authors: Hossein Mohammadhassanzadeh; Karim Oualkacha; Wenmin Zhang; William Klement; Amelie Bourdiec; Jennat Lamsatfi; Yang Yi; Bethany Foster; Paul Keown; Howard M Gebel; Frans Claas; Ruth Sapir-Pichhadze Journal: Kidney Int Rep Date: 2021-03-30