Can Imputation of HLA Allele Level Typing Be Used Clinically in a Multiethnic Population?
1Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, 2Northwestern University, Chicago, IL
Meeting: 2019 American Transplant Congress
Abstract number: 165
Keywords: Allorecognition, Epitopes, HLA antigens
Session Information
Session Name: Concurrent Session: Histocompatibility and Immunogenetics
Session Type: Concurrent Session
Date: Sunday, June 2, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 5:42pm-5:54pm
Location: Room 309
*Purpose: Assignment of eplets in transplantation for the purpose of matching or risk stratification requires high-resolution HLA typing, which is not readily available. Computer algorithms can impute high-resolution type from low-resolution, but the accuracy of these estimates remains unclear.
*Methods: High-resolution HLA typing of 310 subjects, with an ethnic mix of 49% Caucasian, 34% Hispanic, 11% African-American, and 6% Asian, was converted to low-resolution equivalents using the WHO nomenclature. These results were entered into the NMDP HaploStats program and the HLA Matchmaker ConverterVs1 program. Program outputs were then compared to the true, sequence-based high-resolution HLA type.
*Results: The HaploStats software correctly estimated full A, B, DRB1 genotype in 47.1% of the subjects. When the individual loci were analyzed, imputation was more accurate for the A locus (83.2%) than for the DRB1 locus (65.8%). Importantly, overall accuracy varied by ethnicity: 60% for Asians, 57.6% for Caucasians, 34.3% for African-Americans and 33.7% for Hispanics. Similar accuracy (46.1%) was observed when HLA-A, B, C, DRB1, and DQB1 were used to estimate a 5-loci HLA genotype. The HLA Matchmaker ConverterVs1 software was able to return a full result for only 42.9% of all subjects and 35.2% of non-Caucasian subjects. Among those with a complete genotype result, HLA Matchmaker correctly estimated the full A, B, DRB1 genotype in 21.2% of subjects. Accuracy was 59.1% at the A locus, 53.0% at the B locus, and 40.9% at the DRB1 locus. There was minimal variability by ethnicity; accuracy was 24.7% for Caucasians and 25% for non-Caucasians.
*Conclusions: Imputation of HLA antigens for the purpose of deriving high-resolution allele level typing to calculate eplet information is susceptible to a high level of error. This is most evident in Hispanic and African-American populations. Currently, African Americans and Hispanics compose >50% of the patients on the kidney transplant waitlist. Caution should be taken before using imputation tools for clinical or research purposes.
To cite this abstract in AMA style:
Engen RM, Jedraszko AM, Tambur A. Can Imputation of HLA Allele Level Typing Be Used Clinically in a Multiethnic Population? [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/can-imputation-of-hla-allele-level-typing-be-used-clinically-in-a-multiethnic-population/. Accessed May 18, 2025.« Back to 2019 American Transplant Congress