The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these
loci occur with a frequency of about 8%–12% 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 HLA-DRB3/4/5 compatibility and to
correlate the HLA-DRB3/4/5 matching status with the outcome of unrelated
hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their
respective donors were HLA-DRB3/4/5 and HLA-DPB1 typed by amplicon-based nextgeneration
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 HLA-DRB3/4/5 genes were correlated with
clinical outcome. HLA-DRB3/4/5 incompatibility was seen in 12.5% (n = 296) and 17.8%
(n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively. HLA-DRB3/4/5
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 1.02–1.54, p = 0.034] in the otherwise 10/10 HLAmatched
subgroup. The worse outcome was mainly driven by a significantly higher nonrelapse
mortality (HR 1.35, 95% CI 1.05–1.73, 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 HLA-DRB3/4/5 genes significantly impact the outcome
of otherwise fully matched uHSCT and support their consideration upon donor selection in
the future.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84308 |
| Date | 24 March 2023 |
| Creators | Tsamadou, Chrysanthi, Engelhardt, Daphne, Platzbecker, Uwe, Sala, Elisa, Valerius, Thomas, Wagner-Drouet, Eva, Wulf, Gerald, Kröger, Nicolaus, Murawski, Niels, Einsele, Herrmann, Schaefer-Eckart, Kerstin, Freitag, Sebastian, Caspar, Jochen, Kaufmann, Martin, Dürholt, Mareike, Herstenstein, Bernd, Klein, Stefan, Ringhoffer, Mark, Frank, Sandra, Neuchel, Christine, Schrezenmeier, Hubert, Mytilineos, Joannis, Fuerst, Daniel |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1664-3224, 771449 |
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