Researchers from the Departments of Haematology and Public Health and Primary Care, led by Nick Gleadall and Adam Butterworth, have published a study with collaborators in North America, to enable more precise antigen-matching of patients with blood donors. The whole genome sequencing (WGS)-based antigen typing platform provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine.
 
With more than 300 known red blood cell (RBC) antigens and 33 platelet (PLT) antigens that differ between individuals, sensitisation to antigens is a serious complication in prenatal medicine and following blood transfusion, especially for patients requiring multiple transfusions. Recently published in The Lancet Haematology, this collaborative project with Cambridge University, NHS Blood and Transplant, the Wellcome Sanger Institute and collaborators in the US used the MedSeq Project and the INTERVAL study to develop an antigen typing platform that uses WGS data, avoiding the need to conduct costly and laborious serological typing of rare blood antigens. This platform could be used to provide a patient’s care team with much more detailed information on their antigen profile and risk of alloantibody sensitization to aid pre-transfusion antibody identification and donor matching. The WGS typing algorithm was designed using data from 90 MedSeq participants, iteratively improved to address cis–trans haplotype ambiguities and homologous gene alignments, and showed 99.8% concordance. Additional modifications led to the final algorithm, which was 99.2% concordant in a validation set of 200 genomes from INTERVAL blood donors (or 99.9% after adjustment for the lower depth of coverage in the INTERVAL study).
 
The study has led to the creation of a comprehensive antigen allele genotype database and an automated algorithm for WGS-based RBC and PLT antigen typing. This research will ultimately pave the way for routine genetic determination of all key blood group antigens with the potential to transform the way safe blood products are routinely provided to patients. To make the process much more cost-effective, Nick Gleadall is leading the design of a customised genotyping array with the aim to deliver clinical standard concordance but at a fraction of the price of WGS.