Array genotyping of transfusion-relevant blood cell antigens in 6946 ancestrally diverse study participants

Blood transfusions save millions of lives worldwide each year, yet formation of antibodies against nonself antigens remains a significant problem, particularly in patients who receive frequent transfusions. We designed and tested the Universal Blood Donor Typing (UBDT_PC1) array for automated high-throughput simultaneous typing of human erythrocyte antigens (HEAs), platelet antigens (HPAs), leukocyte antigens (HLAs), and neutrophil antigens to support selection of blood products matched beyond ABO/Rh. Typing samples from 6946 study participants of European, African, Admixed American, South Asian, and East Asian ancestry at 2 different laboratories showed a genotype reproducibility of ≥99% for 17 244 variants, translating to 99.98%, 99.90%, and 99.93% concordance across 338 372 HEA, 53 270 HPA, and 107 094 HLA genotypes, respectively. Compared with previous clinical typing data, concordance was 99.9% and 99.6% for 245 874 HEA and 3726 HPA comparisons, respectively. HLA types were 99.1% concordant with clinical typing across 8130 comparisons, with imputation accuracy higher in Europeans vs non-Europeans. Seven variant RHD alleles, a GYPB deletion underlying the U- phenotype, and 14 high-frequency antigen-negative types were also detected. Beyond blood typing, hereditary hemochromatosis-associated HFE variants were identified in 276 participants. We found that the UBDT_PC1 array can reliably type a wide range of blood cell antigens across diverse ancestries. Reproducibility and accuracy were retained when transfusion-relevant targets from the UBDT_PC1 array were incorporated into the UKBB_v2.2 genome-wide typing array. The results represent the potential for significant advancement toward improved patient care by reducing harm in transfusion recipients through extended matching.

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Publication Details

Journal
Blood
Published
2025-06-11
DOI
https://doi.org/10.1182/blood.2025028902
Citations
8
Primary Topic
Blood groups and transfusion
Type
article
Field-Weighted Citation Impact
14.16

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article

Array genotyping of transfusion-relevant blood cell antigens in 6946 ancestrally diverse study participants

Ute Jentsch, David J. Roberts, Olga Shamardina, Jeremy Gollub et al.
8 citations
Blood
Blood groups and transfusion
14.16
article

Array genotyping of transfusion-relevant blood cell antigens in 6946 ancestrally diverse study participants

Ute Jentsch, David J. Roberts, Olga Shamardina, Jeremy Gollub, Emanuele Di Angelantonio, James Daly, Willem H. Ouwehand, Jukka Partanen, Orod Razeghi, Elias Allara, Nathalie Kingston, Sunitha Vege, Nicholas Gleadall, Kati Hyvärinen, William J. Lane, Connie M. Westhoff, C. Ellen van der Schoot, Barbera Veldhuisen, Kathleen Stirrups, Celina Montemayor, Shane Grimsley, Colin Brown, Jonathan Stephens, Aaron J. Gottschalk, Lianne Koets, Ram Varma, Jennifer M. Martin, W. Martin Howell, Gorka Ochoa‐Garay, L. Walker, Andrea Harmer, Shantanu Kaushikkar, Celeste Moya-Valera, John Ord
article en
8 citations

Abstract

Blood transfusions save millions of lives worldwide each year, yet formation of antibodies against nonself antigens remains a significant problem, particularly in patients who receive frequent transfusions. We designed and tested the Universal Blood Donor Typing (UBDT_PC1) array for automated high-throughput simultaneous typing of human erythrocyte antigens (HEAs), platelet antigens (HPAs), leukocyte antigens (HLAs), and neutrophil antigens to support selection of blood products matched beyond ABO/Rh. Typing samples from 6946 study participants of European, African, Admixed American, South Asian, and East Asian ancestry at 2 different laboratories showed a genotype reproducibility of ≥99% for 17 244 variants, translating to 99.98%, 99.90%, and 99.93% concordance across 338 372 HEA, 53 270 HPA, and 107 094 HLA genotypes, respectively. Compared with previous clinical typing data, concordance was 99.9% and 99.6% for 245 874 HEA and 3726 HPA comparisons, respectively. HLA types were 99.1% concordant with clinical typing across 8130 comparisons, with imputation accuracy higher in Europeans vs non-Europeans. Seven variant RHD alleles, a GYPB deletion underlying the U- phenotype, and 14 high-frequency antigen-negative types were also detected. Beyond blood typing, hereditary hemochromatosis-associated HFE variants were identified in 276 participants. We found that the UBDT_PC1 array can reliably type a wide range of blood cell antigens across diverse ancestries. Reproducibility and accuracy were retained when transfusion-relevant targets from the UBDT_PC1 array were incorporated into the UKBB_v2.2 genome-wide typing array. The results represent the potential for significant advancement toward improved patient care by reducing harm in transfusion recipients through extended matching.

BloodVol. 146(12)
Brigham and Women's Hospital (US), University College Hospital (GB), NHS Blood and Transplant (GB), University College London Hospitals NHS Foundation Trust (GB), New York Blood Center (US), Australian Red Cross Lifeblood (AU), Finnish Red Cross (FI), Cambridge University Hospitals NHS Foundation Trust (GB), Sanquin (NL), British Heart Foundation (GB), National Institute for Health and Care Research (GB), South African National Blood Service (ZA), University of Oxford (GB), Bridge University (SS), Cambridge University Health Partners (GB), Human Technopole (IT), Svenskt Stål (Finland) (FI), Wellcome Connecting Science (GB), Thermo Fisher Scientific (United States) (US), INCLIVA Health Research Institute (ES), NIHR BioResource, University College London (GB), Thermo Fisher Scientific (Israel) (IL), Canadian Blood Services (CA)
NHS Blood and Transplant, Australian Government, National Institute for Health and Care Research, British Heart Foundation, Department of Health and Social Care, University of Cambridge, Cambridge University Hospitals, Syöpäsäätiö, Stichting Sanquin Bloedvoorziening, Business Finland, NIHR BioResource, NIHR Cambridge Biomedical Research Centre
Openalex Percentile: Top 1%
Blood groups and transfusion
14.16
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