Array genotyping of transfusion-relevant blood cell antigens in 6946 ancestrally diverse study participants
Abstract
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.
Article Details
Authors (34)
Nicholas S. Gleadall
1Department of Haematology, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
Lianne Koets
3National Screening Laboratory of Sanquin, Sanquin Blood Supply Foundation, Sanquin, Amsterdam, The Netherlands
Olga Shamardina
10Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom
Jeremy Gollub
5Microarray Solutions, Thermo Fisher Scientific, Santa Clara, CA
Aaron J. Gottschalk
6National Center for Blood Group Genomics, New York Blood Center Enterprises, Kansas City, MO
Orod Razeghi
1Department of Haematology, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
Gorka Ochoa-Garay
7Laboratory of Blood Group Genomics, New York Blood Center Enterprises, New York, NY
Jonathan Stephens
1Department of Haematology, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
Ram Varma
5Microarray Solutions, Thermo Fisher Scientific, Santa Clara, CA
Jennifer Martin
1Department of Haematology, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
Elias Allara
1Department of Haematology, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
Colin J. Brown
11Histocompatibility and Immunogenetics, National Health Service Blood and Transplant, London, United Kingdom
James Daly
Emanuele Di Angelantonio
Shane Grimsley
15International Blood Group Reference Laboratory, National Health Service Blood and Transplant, Bristol, United Kingdom
W. Martin Howell
16Histocompatibility and Immunogenetics, National Health Service Blood and Transplant, Newcastle, United Kingdom
Kati Hyvärinen
Ute Jentsch
18South African National Blood Service, Johannesburg, South Africa
Nathalie Kingston
Celina Montemayor
20Red Cell Genomics, Canadian Blood Services, Toronto, Canada
Celeste Moya-Valera
1Department of Haematology, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
John Ord
1Department of Haematology, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
Jukka Partanen
David Roberts
Kathleen E. Stirrups
Sunitha Vege
7Laboratory of Blood Group Genomics, New York Blood Center Enterprises, New York, NY
Lindsay Walker
1Department of Haematology, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
Andrea Harmer
1Department of Haematology, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
Shantanu Kaushikkar
5Microarray Solutions, Thermo Fisher Scientific, Santa Clara, CA
Willem H. Ouwehand
1Department of Haematology, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom
C. Ellen Van der Schoot
6Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands, Amsterdam, Netherlands
Connie M. Westhoff
Barbera Veldhuisen
4Department of Experimental Immunohematology, Sanquin Blood Supply Foundation and Landsteiner Laboratory, Amsterdam University Medical Center, Amsterdam, The Netherlands
William J. Lane
29Department of Pathology, Brigham and Women’s Hospital, Boston, MA