{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:48:05Z","timestamp":1793386085755,"version":"4.5.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012331","name":"Agentschap Innoveren en Ondernemen","doi-asserted-by":"publisher","award":["IWT.150199"],"award-info":[{"award-number":["IWT.150199"]}],"id":[{"id":"10.13039\/100012331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"FWO","doi-asserted-by":"publisher","award":["1844019N"],"award-info":[{"award-number":["1844019N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"FWO","doi-asserted-by":"publisher","award":["1842919N"],"award-info":[{"award-number":["1842919N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"FWO","doi-asserted-by":"publisher","award":["1143919N"],"award-info":[{"award-number":["1143919N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"FWO","doi-asserted-by":"publisher","award":["1196119N"],"award-info":[{"award-number":["1196119N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leaven","doi-asserted-by":"publisher","award":["C32\/17\/049"],"award-info":[{"award-number":["C32\/17\/049"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2020,9]]},"abstract":"\n Significance Statement<\/jats:title>\n \n HLA matching for three HLA loci (HLA-A, HLA-B, and HLA-DR) at a low-resolution antigen level has been integral to algorithms for allocating donor kidneys for transplant since the 1970s. The authors used high-resolution genotyping of the 11 HLA loci and analysis of mismatches of HLA eplets\u2014small patches of surface-exposed amino acids of the HLA molecule\u2014to evaluate the effect of eplet mismatches on\n de novo<\/jats:italic>\n formation of donor-specific HLA antibodies (DSAs) and kidney transplant outcome. They found that eplet mismatches in the HLA-DQ locus are most important for DSA formation, rejection, decline of graft function, and graft failure. Their findings suggest that molecular HLA-DQ matching might be more helpful than antigen matching for HLA-A, HLA-B, and HLA-DR when aiming to minimize formation of DSAs and improve outcomes after transplant.\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n In kidney transplantation, evaluating mismatches of HLA eplets\u2014small patches of surface-exposed amino acids of the HLA molecule\u2014instead of antigen mismatches might offer a better approach to assessing donor-recipient HLA incompatibility and improve risk assessment and prediction of transplant outcomes.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n To evaluate the effect of number of eplet mismatches (mismatch load) on\n de novo<\/jats:italic>\n formation of donor-specific HLA antibodies (DSAs) and transplant outcomes, we conducted a cohort study that included consecutive adult kidney recipients transplanted at a single center from March 2004 to February 2013. We performed retrospective high-resolution genotyping of HLA loci of 926 transplant pairs and used the HLAMatchmaker computer algorithm to count HLA eplet mismatches.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n De novo<\/jats:italic>\n DSAs occurred in 43 (4.6%) patients. Multivariable analysis showed a significant independent association between antibody-verified eplet mismatch load and\n de novo<\/jats:italic>\n DSA occurrence and graft failure, mainly explained by DQ antibody-verified eplet effects. The association with DQ antibody-verified eplet mismatches was linear, without a safe threshold at which\n de novo<\/jats:italic>\n DSA did not occur. Odds for T cell\u2013 or antibody-mediated rejection increased by 5% and 12%, respectively, per antibody-verified DQ eplet mismatch.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Eplet mismatches in HLA-DQ confer substantial risk for\n de novo<\/jats:italic>\n DSA formation, graft rejection, and graft failure after kidney transplantation. Mismatches in other loci seem to have less effect. The results suggest that antibody-verified HLA-DQ eplet mismatch load could be used to guide personalized post-transplant immunosuppression. Adoption of molecular matching for DQA\n 1<\/jats:sub>\n and DQB\n 1<\/jats:sub>\n alleles could also help to minimize\n de novo<\/jats:italic>\n DSA formation and potentially improve transplant outcomes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2020010019","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T20:45:41Z","timestamp":1596746741000},"page":"2193-2204","source":"Crossref","is-referenced-by-count":193,"title":["Eplet Mismatch Load and De Novo Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort Study"],"prefix":"10.1681","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6196-4669","authenticated-orcid":false,"given":"Aleksandar","family":"Senev","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium"},{"name":"Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross\u2014Flanders, Mechelen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Coemans","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium"},{"name":"Department of Public Health and Primary Care, Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Lerut","sequence":"additional","affiliation":[{"name":"Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky","family":"Van Sandt","sequence":"additional","affiliation":[{"name":"Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross\u2014Flanders, Mechelen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Kerkhofs","sequence":"additional","affiliation":[{"name":"Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross\u2014Flanders, Mechelen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9191-4590","authenticated-orcid":false,"given":"Liesbeth","family":"Dani\u00ebls","sequence":"additional","affiliation":[{"name":"Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross\u2014Flanders, Mechelen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen Vanden","family":"Driessche","sequence":"additional","affiliation":[{"name":"Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross\u2014Flanders, Mechelen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Compernolle","sequence":"additional","affiliation":[{"name":"Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross\u2014Flanders, Mechelen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Sprangers","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9796-9157","authenticated-orcid":false,"given":"Elisabet","family":"Van Loon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Callemeyn","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans","family":"Claas","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat R.","family":"Tambur","sequence":"additional","affiliation":[{"name":"Transplant Immunology Laboratory, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Verbeke","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Kuypers","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Paule","family":"Emonds","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium"},{"name":"Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross\u2014Flanders, Mechelen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5625-0792","authenticated-orcid":false,"given":"Maarten","family":"Naesens","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJMra0902927","article-title":"Rejection of the kidney allograft","volume":"363","author":"Nankivell","year":"2010","journal-title":"N Engl J 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