{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T07:43:54Z","timestamp":1793519034002,"version":"4.5.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["Grant No 2018.092.1"],"award-info":[{"award-number":["Grant No 2018.092.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The<jats:italic>HLA-DRB3\/4\/5<\/jats:italic>loci are closely linked to the<jats:italic>HLA-DRB1<\/jats:italic>gene. Mismatches in these loci occur with a frequency of about 8%\u201312% in otherwise 10\/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large cohort of German patients and their donors for<jats:italic>HLA-DRB3\/4\/5<\/jats:italic>compatibility and to correlate the<jats:italic>HLA-DRB3\/4\/5<\/jats:italic>matching status with the outcome of unrelated hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their respective donors were<jats:italic>HLA-DRB3\/4\/5<\/jats:italic>and<jats:italic>HLA-DPB1<\/jats:italic>typed by amplicon-based next-generation sequencing (NGS). All patients included received their first allogeneic transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in the antigen recognition domain (ARD) of<jats:italic>HLA-DRB3\/4\/5<\/jats:italic>genes were correlated with clinical outcome.<jats:italic>HLA-DRB3\/4\/5<\/jats:italic>incompatibility was seen in 12.5% (n = 296) and 17.8% (n = 185) of the 10\/10 and 9\/10 HLA-matched cases, respectively.<jats:italic>HLA-DRB3\/4\/5<\/jats:italic>mismatches in the ARD associated with a worse overall survival (OS), as shown in univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses [hazard ratio (HR) 1.25, 95% CI 1.02\u20131.54, p = 0.034] in the otherwise 10\/10 HLA-matched subgroup. The worse outcome was mainly driven by a significantly higher non-relapse mortality (HR 1.35, 95% CI 1.05\u20131.73, p = 0.017). In the 9\/10 HLA-matched cases, the effect was not statistically significant. Our study results suggest that mismatches within the ARD of<jats:italic>HLA-DRB3\/4\/5<\/jats:italic>genes significantly impact the outcome of otherwise fully matched uHSCT and support their consideration upon donor selection in the future.<\/jats:p>","DOI":"10.3389\/fimmu.2021.771449","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T09:23:16Z","timestamp":1639473796000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["HLA-DRB3\/4\/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation"],"prefix":"10.3389","volume":"12","author":[{"given":"Chrysanthi","family":"Tsamadou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne","family":"Engelhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Platzbecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Sala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Valerius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Wagner-Drouet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Wulf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaus","family":"Kr\u00f6ger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Murawski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Einsele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Schaefer-Eckart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Freitag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Casper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike","family":"D\u00fcrholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Hertenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ringhoffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Neuchel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Schrezenmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joannis","family":"Mytilineos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Fuerst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.21.7197","article-title":"Linkage Map of Three HLA-DR Beta-Chain Genes: Evidence for a Recent Duplication Event","volume":"82","author":"Rollini","year":"1985","journal-title":"Proc Natl Acad Sci USA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2007.04.005","article-title":"High-Resolution HLA Alleles and Haplotypes in the United States Population","volume":"68","author":"Maiers","year":"2007","journal-title":"Hum Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/BF00430597","article-title":"Allostimulating Cells in Man. 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