Development and validation of a universal blood donor genotyping platform: A multinational prospective study

NIHR BioResource, Blood Transfusion Genomics Consortium

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non-self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates. This DNA-based test is capable of simultaneously typing most clinically relevant red blood cell (RBC), human platelet (HPA), and human leukocyte (HLA) antigens. Validation was performed, using samples from 7927 European, 27 South Asian, 21 East Asian, and 9 African blood donors enrolled in 2 national biobanks. We illustrated the usefulness of the platform by analyzing antibody data from patients sensitized with multiple RBC alloantibodies. Genotyping results demonstrated concordance of 99.91%, 99.97%, and 99.03% with RBC, HPA, and HLA clinically validated typing results in 89 371, 3016, and 9289 comparisons, respectively. Genotyping increased the total number of antigen typing results available from 110 980 to >1 200 000. Dense donor typing allowed identification of 2 to 6 times more compatible donors to serve 3146 patients with multiple RBC alloantibodies, providing at least 1 match for 176 individuals for whom previously no blood could be found among the same donors. This genotyping technology is already being used to type thousands of donors taking part in national genotyping studies. Extraction of dense antigen-typing data from these cohorts provides blood supply organizations with the opportunity to implement a policy of genomics-based precision matching of blood.

Original languageEnglish
Pages (from-to)3495-3506
Number of pages12
JournalBlood Advances
Volume4
Issue number15
DOIs
Publication statusPublished - 11 Aug 2020
Externally publishedYes

Bibliographical note

Funding Information:
Funding for the project was provided by NHSBT, NIHR (grant RG65966) and Sanquin (grant PPOC 14-028). The Academic Coordinating Centre for the COMPARE and INTERVAL studies was supported by core funding from the NIHR Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics (grant NIHR BTRU-2014-10024), the UK Medical Research Council (MRC; grant MR/L003120/1), the British Heart Foundation (grants SP/09/ 002; RG/13/13/30194; RG/18/13/33946), and the NIHR (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). This work also made use of the UKBB resource under application 13745 and received support from Health Data Research UK, which is funded by the MRC, the Engineering and Physical Sciences Research Council, the Economic and Social

Funding Information:
Research Council, the Department of Health and Social Care (England), the Chief Scientist Office of the Scottish Government Health and Social Care Directorates, the Health and Social Care Research and Development Division (Welsh Government), the Public Health Agency (Northern Ireland), the British Heart Foundation, and the Wellcome Trust. Participants in the COMPARE and INTERVAL trials were recruited with the active collaboration of NHSBT, which supported field work and other elements of the trial. DNA extraction and genotyping was cofunded by the NIHR BioResource and the NIHR, via the Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust.

Funding Information:
The Academic Coordinating Centre thanks the Blood Donor Centre staff and blood donors for participating in this study. This study made use of data generated by the COMPARE and DIS-III studies. Genotyping results for COMPARE participants were retrieved from the NIHR BioResource. The authors thank NIHR BioResource volunteers for their participation; NIHR BioResource Centres, NHS Trusts, and NHS Blood and Transplant (NHSBT) and staff for their contribution; the Locus Reference Genomic team at the EBI for their assistance in curating gene transcripts; and all colleagues, in particular, Alan Gray and Candice Davidson (NHSBT Tooting Centre, London, United Kingdom) for scientific and clinical advice. Funding for the project was provided by NHSBT, NIHR (grant RG65966) and Sanquin (grant PPOC 14-028). The Academic Coordinating Centre for the COMPARE and INTERVAL studies was supported by core funding from the NIHR Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics (grant NIHR BTRU-2014-10024), the UK Medical Research Council (MRC; grant MR/L003120/1), the British Heart Foundation (grants SP/09/ 002; RG/13/13/30194; RG/18/13/33946), and the NIHR (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). This work also made use of the UKBB resource under application 13745 and received support from Health Data Research UK,which is funded by the MRC, the Engineering and Physical Sciences Research Council, the Economic and Social ResearchCouncil, theDepartment ofHealth andSocialCare (England), theChief ScientistOffice of the Scottish Government Health andSocial Care Directorates, the Health and Social Care Research and Development Division (Welsh Government), the Public Health Agency (Northern Ireland), the British Heart Foundation, and the Wellcome Trust. Participants in the COMPARE and INTERVAL trials were recruited with the active collaboration of NHSBT, which supported fieldwork and other elements of the trial.DNAextraction and genotyping was cofunded by the NIHR BioResource and the NIHR, via the Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust. Complete lists of the investigators and contributors to the INTERVAL andCOMPAREstudies havebeenpublished (Lancet. 2017;390(10110): 2360-2371 and ISRCTN Registry 2017;ISRCTN90871183). The views expressed are those of the authors and are not necessarily those of the NHS, NIHR, or the Department of Health and Social Care in England.

Publisher Copyright:
© 2020 American Society of Hematology. All rights reserved.

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