Tran, JN;
Gunther, OP;
Sherwood, KR;
Fenninger, F;
Allan, LL;
Lan, J;
Sapir-Pichhadze, R;
... Keown, PA; + view all
(2021)
High-throughput sequencing defines donor and recipient HLA B-cell epitope frequencies for prospective matching in transplantation.
Communications Biology
, 4
(1)
, Article 583. 10.1038/s42003-021-01989-3.
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High-throughput sequencing defines donor and recipient HLA B-cell epitope frequencies for prospective matching in transplant.pdf - Published Version Download (4MB) | Preview |
Abstract
Compatibility for human leukocyte antigen (HLA) genes between transplant donors and recipients improves graft survival but prospective matching is rarely performed due to the vast heterogeneity of this gene complex. To reduce complexity, we have combined next-generation sequencing and in silico mapping to determine transplant population frequencies and matching probabilities of 150 antibody-binding eplets across all 11 classical HLA genes in 2000 ethnically heterogeneous renal patients and donors. We show that eplets are more common and uniformly distributed between donors and recipients than the respective HLA isoforms. Simulations of targeted eplet matching shows that a high degree of overall compatibility, and perfect identity at the clinically important HLA class II loci, can be obtained within a patient waiting list of approximately 250 subjects. Internal epitope-based allocation is thus feasible for most major renal transplant programs, while regional or national sharing may be required for other solid organs.
| Type: | Article |
|---|---|
| Title: | High-throughput sequencing defines donor and recipient HLA B-cell epitope frequencies for prospective matching in transplantation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s42003-021-01989-3 |
| Publisher version: | https://doi.org/10.1038/s42003-021-01989-3 |
| Language: | English |
| Additional information: | © 2021 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Allotransplantation, Immunogenetics, Molecular medicine, Population genetics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10138261 |
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