{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:19:02Z","timestamp":1772641142119,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009248","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000}}],"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>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<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.pirche.com\/\" xlink:type=\"simple\">www.pirche.com<\/jats:ext-link>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.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009248","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T17:30:11Z","timestamp":1627407011000},"page":"e1009248","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3514-9812","authenticated-orcid":true,"given":"Matthias","family":"Niemann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2081-3098","authenticated-orcid":true,"given":"Nils","family":"Lachmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten","family":"Geneugelijk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Spierings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"issue":"3","key":"pcbi.1009248.ref001","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1097\/TP.0b013e31827d62e3","article-title":"Incidence and impact of de novo donor-specific alloantibody in primary renal allografts","volume":"95","author":"MJ Everly","year":"2013","journal-title":"Transplantation"},{"issue":"3","key":"pcbi.1009248.ref002","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1097\/TP.0b013e31817c4cb8","article-title":"Human leukocyte antigen antibodies and chronic rejection: from association to causation","volume":"86","author":"PI Terasaki","year":"2008","journal-title":"Transplantation"},{"issue":"5","key":"pcbi.1009248.ref003","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1097\/01.TP.0000155246.52249.AC","article-title":"Development of posttransplant antidonor HLA antibodies is associated with acute humoral rejection and early graft dysfunction","volume":"79","author":"Q Zhang","year":"2005","journal-title":"Transplantation"},{"issue":"8","key":"pcbi.1009248.ref004","first-page":"793","article-title":"Human leukocyte antigen matching in heart transplantation: systematic review and meta-analysis","volume":"27","author":"D Ansari","year":"2014","journal-title":"Transpl Int Off J Eur Soc Organ Transplant"},{"issue":"4","key":"pcbi.1009248.ref005","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1097\/MOT.0b013e3283636ddf","article-title":"Current role of human leukocyte antigen matching in kidney transplantation","volume":"18","author":"C S\u00fcsal","year":"2013","journal-title":"Curr Opin Organ Transplant"},{"issue":"4","key":"pcbi.1009248.ref006","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1097\/01.TP.0000103725.72023.D7","article-title":"It takes six to boogie: allocating cadaver kidneys in Eurotransplant","volume":"77","author":"IIN Doxiadis","year":"2004","journal-title":"Transplantation"},{"issue":"6","key":"pcbi.1009248.ref007","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.humimm.2006.03.008","article-title":"Allocation of organs, particularly kidneys, within Eurotransplant","volume":"67","author":"GG Persijn","year":"2006","journal-title":"Hum Immunol"},{"issue":"3\u20134","key":"pcbi.1009248.ref008","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.trim.2005.03.007","article-title":"Differential immunogenicity of HLA mismatches in clinical transplantation","volume":"14","author":"FHJ Claas","year":"2005","journal-title":"Transpl Immunol"},{"issue":"9031","key":"pcbi.1009248.ref009","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/S0140-6736(96)02296-9","article-title":"Association between specific HLA combinations and probability of kidney allograft loss: the taboo concept","volume":"348","author":"II Doxiadis","year":"1996","journal-title":"Lancet Lond Engl"},{"issue":"1","key":"pcbi.1009248.ref010","first-page":"2","article-title":"Eurotransplant kidney allocation system (ETKAS): rationale and implementation","volume":"21","author":"G Mayer","year":"2006","journal-title":"Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc\u2014Eur Ren Assoc"},{"key":"pcbi.1009248.ref011","unstructured":"Eurotransplant Foundation. 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In: 2019 Winter Simulation Conference (WSC) [Internet]. National Harbor, MD, USA: IEEE; 2019 [cited 2020 Nov 10]. p. 1079\u201390. 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