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Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation.
Am J Transplant. 2020 May 20 [Online ahead of print]AJ

Abstract

Molecular mismatch analysis for assessment of histocompatibility in transplantation requires high-resolution HLA typing. Algorithms to "guesstimate" high-resolution from low-resolution typing exist, but their accuracy remains unknown. We converted high-resolution, sequence-based, HLA typing of 310 subjects from an ethnically heterogeneous population to low-resolution equivalents and tested the ability of the NMDP HaploStats and HLA Matchmaker programs to impute/reproduce the measured high-resolution HLA type, using the more common "winner-takes-all" approach. Only 35.6% of the HaploStats imputed HLA-A, -B, -C, -DRB1, and -DQB1 haplotypes had no mistakes, and the accuracy was significantly lower for non-Caucasians (29.1%) compared to Caucasians (45.2%) (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3-0.8; P = .004). HLA Matchmaker was not able to provide high-resolution haplotypes for 45.2% of Caucasian subjects and 63.5% of non-Caucasian subjects (P = .002). Of those with an imputed result, only 10.3% of Caucasians and 4.8% of non-Caucasians had accurate 10-allele high-resolution output. Eplet analysis revealed additional, inaccurate eplets in 37% of individuals, with 22.5% showing at least 2 additional, inaccurate eplets; incorrect eplets were more common among non-Caucasians (OR, 1.8; 95% CI, 1.1-2.9; P = .018). Given this high error rate, caution should be taken before using imputation tools for clinical or research purposes, especially for non-Caucasian individuals.

Authors+Show Affiliations

Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.Stanley Manne Children's Research Institute, Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32430947

Citation

Engen, Rachel M., et al. "Substituting Imputation of HLA Antigens for High-resolution HLA Typing: Evaluation of a Multiethnic Population and Implications for Clinical Decision Making in Transplantation." American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2020.
Engen RM, Jedraszko AM, Conciatori MA, et al. Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation. Am J Transplant. 2020.
Engen, R. M., Jedraszko, A. M., Conciatori, M. A., & Tambur, A. R. (2020). Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. https://doi.org/10.1111/ajt.16070
Engen RM, et al. Substituting Imputation of HLA Antigens for High-resolution HLA Typing: Evaluation of a Multiethnic Population and Implications for Clinical Decision Making in Transplantation. Am J Transplant. 2020 May 20; PubMed PMID: 32430947.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation. AU - Engen,Rachel M, AU - Jedraszko,Aneta M, AU - Conciatori,Michael A, AU - Tambur,Anat R, Y1 - 2020/05/20/ PY - 2019/12/13/received PY - 2020/04/09/revised PY - 2020/04/30/accepted PY - 2020/5/21/pubmed PY - 2020/5/21/medline PY - 2020/5/21/entrez KW - clinical research/ practice KW - histocompatibility KW - kidney transplantation/ nephrology KW - major histocompatibility complex (MHC) KW - organ allocation KW - organ procurement and allocation KW - risk assessment/ risk stratification JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JO - Am. J. Transplant. N2 - Molecular mismatch analysis for assessment of histocompatibility in transplantation requires high-resolution HLA typing. Algorithms to "guesstimate" high-resolution from low-resolution typing exist, but their accuracy remains unknown. We converted high-resolution, sequence-based, HLA typing of 310 subjects from an ethnically heterogeneous population to low-resolution equivalents and tested the ability of the NMDP HaploStats and HLA Matchmaker programs to impute/reproduce the measured high-resolution HLA type, using the more common "winner-takes-all" approach. Only 35.6% of the HaploStats imputed HLA-A, -B, -C, -DRB1, and -DQB1 haplotypes had no mistakes, and the accuracy was significantly lower for non-Caucasians (29.1%) compared to Caucasians (45.2%) (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3-0.8; P = .004). HLA Matchmaker was not able to provide high-resolution haplotypes for 45.2% of Caucasian subjects and 63.5% of non-Caucasian subjects (P = .002). Of those with an imputed result, only 10.3% of Caucasians and 4.8% of non-Caucasians had accurate 10-allele high-resolution output. Eplet analysis revealed additional, inaccurate eplets in 37% of individuals, with 22.5% showing at least 2 additional, inaccurate eplets; incorrect eplets were more common among non-Caucasians (OR, 1.8; 95% CI, 1.1-2.9; P = .018). Given this high error rate, caution should be taken before using imputation tools for clinical or research purposes, especially for non-Caucasian individuals. SN - 1600-6143 UR - https://www.unboundmedicine.com/medline/citation/32430947/Substituting_imputation_of_HLA_antigens_for_high_resolution_HLA_typing:_Evaluation_of_a_multiethnic_population_and_implications_for_clinical_decision_making_in_transplantation L2 - https://doi.org/10.1111/ajt.16070 DB - PRIME DP - Unbound Medicine ER -
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