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The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis

Authors :
Daphne Mytilineos
Chrysanthi Tsamadou
Christine Neuchel
Uwe Platzbecker
Donald Bunjes
Natalie Schub
Eva Wagner-Drouet
Gerald Wulf
Nicolaus Kröger
Niels Murawski
Hermann Einsele
Kerstin Schaefer-Eckart
Sebastian Freitag
Jochen Casper
Martin Kaufmann
Mareike Dürholt
Bernd Hertenstein
Stefan Klein
Mark Ringhoffer
Carlheinz R. Mueller
Sandra Frank
Hubert Schrezenmeier
Daniel Fuerst
Joannis Mytilineos
Source :
Frontiers in Immunology, Vol 11 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

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.

Details

Language :
English
ISSN :
16643224
Volume :
11
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.8dbb750c2243f7b3fbc668a0b83d84
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2020.614976