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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.

Research paper by Daphne D Mytilineos, Chrysanthi C Tsamadou, Christine C Neuchel, Uwe U Platzbecker, Donald D Bunjes, Natalie N Schub, Eva E Wagner-Drouet, Gerald G Wulf, Nicolaus N Kröger, Niels N Murawski, Hermann H Einsele, Kerstin K Schaefer-Eckart, Sebastian S Freitag, Jochen J Casper, Martin M Kaufmann, et al.

Indexed on: 12 Feb '21Published on: 12 Feb '21Published in: Frontiers in immunology



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. Copyright © 2021 Mytilineos, Tsamadou, Neuchel, Platzbecker, Bunjes, Schub, Wagner-Drouet, Wulf, Kröger, Murawski, Einsele, Schaefer-Eckart, Freitag, Casper, Kaufmann, Dürholt, Hertenstein, Klein, Ringhoffer, Mueller, Frank, Schrezenmeier, Fuerst and Mytilineos.

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