Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation

Rachel M. Engen*, Aneta M. Jedraszko, Michael A. Conciatori, Anat Roitberg-Tambur

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
JournalAmerican Journal of Transplantation
DOIs
StateAccepted/In press - 2020

Keywords

  • clinical research/ practice
  • histocompatibility
  • kidney transplantation/ nephrology
  • major histocompatibility complex (MHC)
  • organ allocation
  • organ procurement and allocation
  • risk assessment/ risk stratification

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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