Tran, J;
Gunther, O;
Sherwood, K;
Fenninger, F;
Allan, L;
Lan, J;
Sapir-Pichhadze, R;
... Keown, P; + view all
(2020)
Population Frequencies Determined by Next-generation Sequencing Provide Strategies for Prospective HLA Epitope Matching for Transplantation.
Research Square: Durham, NC, USA.
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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 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 more uniformly distributed between donors and recipients than the respective HLA isoforms. Simulation 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: | Working / discussion paper |
|---|---|
| Title: | Population Frequencies Determined by Next-generation Sequencing Provide Strategies for Prospective HLA Epitope Matching for Transplantation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.21203/rs.3.rs-50893/v1 |
| Publisher version: | https://doi.org/10.21203/rs.3.rs-50893/v1 |
| Language: | English |
| Additional information: | This work is licensed under a CC BY 4.0 License (https://creativecommons.org/licenses/by/4.0/) |
| Keywords: | HLA epitopes, antibody-verified, HLA alleles, next-generation sequencing, biomarkers, kidney transplantation |
| 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.ucl.ac.uk/id/eprint/10138238 |
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