The human leukocyte antigen-DPB1 degree of compatibility is determined by its expression level and mismatch permissiveness: a german multicenter analysis

peer-reviewed
Erstveröffentlichung
2021-01-25Authors
Mytilineos, Daphne
Tsamadou, Chrysanthi
Neuchel, Christine
Platzbecker, Uwe
Bunjes, Donald
Wissenschaftlicher Artikel
Published in
Frontiers in Immunology ; 11 (2021). - Art.-Nr. 3389. - eISSN 1664-3224
Link to original publication
https://dx.doi.org/10.3389/fimmu.2020.614976Institutions
Institut für Klinische Transfusionsmedizin und Immungenetik Ulm gGmbH (IKT)UKU. Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie
UKU. Institut für Transfusionsmedizin
UKU. Klinik für Innere Medizin III
Document version
published version (publisher's PDF)Abstract
T-cell epitope matching according to the TCE3 algorithm classifies HLA-DPB1 mismatches in permissive and non-permissive. This classification has been shown to be predictive for mortality and acute GvHD (aGvHD) events in large international cohorts. We retrospectively genotyped HLA-DPB1 in 3523 patients transplanted in Germany between 2000 and 2014 and in their unrelated donors using an Illumina amplicon-NGS based assay. Aim of the study was to evaluate DP-compatibility beyond the established TCE3 algorithm by assessing the combined effect of several DP-mismatch parameters on post-transplant outcome. We implemented an extended DP-mismatch assessment model where TCE3, DP allotype expression with respect to rs9277534, mismatch vector and number of mismatches were conjointly taken into consideration. In this model, non-permissive HLA-DPB1 mismatches showed significantly increased aGvHD risk if they were accompanied by two HLA-DPB1 mismatches in GvH direction (HR: 1.46) or one mismatched highly expressed patient allotype (HR: 1.53). As previously reported, non-permissive HLA-DPB1 mismatches associated with a significantly higher risk of aGvHD and non-relapse mortality (HR 1.36 and 1.21, respectively), which in turn translated into worse GvHD and relapse free survival (HR 1.13). Effects on GvL and GvHD appeared strongest in GvH-directed non-permissive mismatches. Our study results support the consideration of additional HLA-DPB1 mismatch parameters along with the established TCE3 matching algorithm for refinement of future donor selection. In particular, our findings suggest that DP non-permissiveness associated with two HLA-DPB1 mismatches or at least on highly expressed mismatched patient allotype should be avoided.
Is supplemented by
https://www.frontiersin.org/articles/10.3389/fimmu.2020.614976/full#supplementary-materialSubject headings
[GND]: Periphere Stammzellentransplantation | Transplantat-Wirt-Reaktion[MeSH]: Stem cell transplantation | Graft vs host disease
[Free subject headings]: graft-versus-host-disease | HLA-DPB1 | HLA-DPB1 expression | HLA-DPB1-permissiveness
[DDC subject group]: DDC 610 / Medicine & health
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Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-43533
Mytilineos, Daphne et al. (2022): The human leukocyte antigen-DPB1 degree of compatibility is determined by its expression level and mismatch permissiveness: a german multicenter analysis. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-43533
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