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

  • 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

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.

Bibliografische Daten

OriginalspracheEnglisch
Aufsatznummer614976
ISSN1664-3224
DOIs
StatusVeröffentlicht - 2020

Anmerkungen des Dekanats

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.

PubMed 33569061