Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching.

The EuroTransplant Kidney Allocation System (ETKAS) aims at allocating organs to patients on the waiting list fairly whilst optimizing HLA match grades. ETKAS currently considers the number of HLA-A, -B, -DR mismatches. Evidently, epitope matching is biologically and clinically more relevant. We her...

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Autores principales:	Matthias Niemann, Nils Lachmann, Kirsten Geneugelijk, Eric Spierings
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/906fa0f267b24e0b8042e575073c0d4f
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spelling	oai:doaj.org-article:906fa0f267b24e0b8042e575073c0d4f2021-12-02T19:57:22ZComputational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching.1553-734X1553-735810.1371/journal.pcbi.1009248https://doaj.org/article/906fa0f267b24e0b8042e575073c0d4f2021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009248https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The EuroTransplant Kidney Allocation System (ETKAS) aims at allocating organs to patients on the waiting list fairly whilst optimizing HLA match grades. ETKAS currently considers the number of HLA-A, -B, -DR mismatches. Evidently, epitope matching is biologically and clinically more relevant. We here executed ETKAS-based computer simulations to evaluate the impact of epitope matching on allocation and compared the strategies. A virtual population of 400,000 individuals was generated using the National Marrow Donor Program (NMDP) haplotype frequency dataset of 2011. Using this population, a waiting list of 10,400 patients was constructed and maintained during simulation, matching the 2015 Eurotransplant Annual Report characteristics. Unacceptable antigens were assigned randomly relative to their frequency using HLAMatchmaker. Over 22,600 kidneys were allocated in 10 years in triplicate using Markov Chain Monte Carlo simulations on 32-CPU-core cloud-computing instances. T-cell epitopes were calculated using the www.pirche.com portal. Waiting list effects were evaluated against ETKAS for five epitope matching scenarios. Baseline simulations of ETKAS slightly overestimated reported average HLA match grades. The best balanced scenario maintained prioritisation of HLA A-B-DR fully matched donors while replacing the HLA match grade by PIRCHE-II score and exchanging the HLA mismatch probability (MMP) by epitope MMP. This setup showed no considerable impact on kidney exchange rates and waiting time. PIRCHE-II scores improved, whereas the average HLA match grade diminishes slightly, yet leading to an improved estimated graft survival. We conclude that epitope-based matching in deceased donor kidney allocation is feasible while maintaining equal balances on the waiting list.Matthias NiemannNils LachmannKirsten GeneugelijkEric SpieringsPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 7, p e1009248 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Matthias Niemann Nils Lachmann Kirsten Geneugelijk Eric Spierings Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching.
description	The EuroTransplant Kidney Allocation System (ETKAS) aims at allocating organs to patients on the waiting list fairly whilst optimizing HLA match grades. ETKAS currently considers the number of HLA-A, -B, -DR mismatches. Evidently, epitope matching is biologically and clinically more relevant. We here executed ETKAS-based computer simulations to evaluate the impact of epitope matching on allocation and compared the strategies. A virtual population of 400,000 individuals was generated using the National Marrow Donor Program (NMDP) haplotype frequency dataset of 2011. Using this population, a waiting list of 10,400 patients was constructed and maintained during simulation, matching the 2015 Eurotransplant Annual Report characteristics. Unacceptable antigens were assigned randomly relative to their frequency using HLAMatchmaker. Over 22,600 kidneys were allocated in 10 years in triplicate using Markov Chain Monte Carlo simulations on 32-CPU-core cloud-computing instances. T-cell epitopes were calculated using the www.pirche.com portal. Waiting list effects were evaluated against ETKAS for five epitope matching scenarios. Baseline simulations of ETKAS slightly overestimated reported average HLA match grades. The best balanced scenario maintained prioritisation of HLA A-B-DR fully matched donors while replacing the HLA match grade by PIRCHE-II score and exchanging the HLA mismatch probability (MMP) by epitope MMP. This setup showed no considerable impact on kidney exchange rates and waiting time. PIRCHE-II scores improved, whereas the average HLA match grade diminishes slightly, yet leading to an improved estimated graft survival. We conclude that epitope-based matching in deceased donor kidney allocation is feasible while maintaining equal balances on the waiting list.
format	article
author	Matthias Niemann Nils Lachmann Kirsten Geneugelijk Eric Spierings
author_facet	Matthias Niemann Nils Lachmann Kirsten Geneugelijk Eric Spierings
author_sort	Matthias Niemann
title	Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching.
title_short	Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching.
title_full	Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching.
title_fullStr	Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching.
title_full_unstemmed	Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching.
title_sort	computational eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of t-cell epitope matching.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/906fa0f267b24e0b8042e575073c0d4f
work_keys_str_mv	AT matthiasniemann computationaleurotransplantkidneyallocationsimulationsdemonstratethefeasibilityandbenefitoftcellepitopematching AT nilslachmann computationaleurotransplantkidneyallocationsimulationsdemonstratethefeasibilityandbenefitoftcellepitopematching AT kirstengeneugelijk computationaleurotransplantkidneyallocationsimulationsdemonstratethefeasibilityandbenefitoftcellepitopematching AT ericspierings computationaleurotransplantkidneyallocationsimulationsdemonstratethefeasibilityandbenefitoftcellepitopematching
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Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching.

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