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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

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 patie...

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Autores principales: Mytilineos, Daphne, Tsamadou, Chrysanthi, Neuchel, Christine, Platzbecker, Uwe, Bunjes, Donald, Schub, Natalie, Wagner-Drouet, Eva, Wulf, Gerald, Kröger, Nicolaus, Murawski, Niels, Einsele, Hermann, Schaefer-Eckart, Kerstin, Freitag, Sebastian, Casper, Jochen, Kaufmann, Martin, Dürholt, Mareike, Hertenstein, Bernd, Klein, Stefan, Ringhoffer, Mark, Mueller, Carlheinz R., Frank, Sandra, Schrezenmeier, Hubert, Fuerst, Daniel, Mytilineos, Joannis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868530/
https://www.ncbi.nlm.nih.gov/pubmed/33569061
http://dx.doi.org/10.3389/fimmu.2020.614976
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author Mytilineos, Daphne
Tsamadou, Chrysanthi
Neuchel, Christine
Platzbecker, Uwe
Bunjes, Donald
Schub, Natalie
Wagner-Drouet, Eva
Wulf, Gerald
Kröger, Nicolaus
Murawski, Niels
Einsele, Hermann
Schaefer-Eckart, Kerstin
Freitag, Sebastian
Casper, Jochen
Kaufmann, Martin
Dürholt, Mareike
Hertenstein, Bernd
Klein, Stefan
Ringhoffer, Mark
Mueller, Carlheinz R.
Frank, Sandra
Schrezenmeier, Hubert
Fuerst, Daniel
Mytilineos, Joannis
author_facet Mytilineos, Daphne
Tsamadou, Chrysanthi
Neuchel, Christine
Platzbecker, Uwe
Bunjes, Donald
Schub, Natalie
Wagner-Drouet, Eva
Wulf, Gerald
Kröger, Nicolaus
Murawski, Niels
Einsele, Hermann
Schaefer-Eckart, Kerstin
Freitag, Sebastian
Casper, Jochen
Kaufmann, Martin
Dürholt, Mareike
Hertenstein, Bernd
Klein, Stefan
Ringhoffer, Mark
Mueller, Carlheinz R.
Frank, Sandra
Schrezenmeier, Hubert
Fuerst, Daniel
Mytilineos, Joannis
author_sort Mytilineos, Daphne
collection PubMed
description 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.
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spelling pubmed-78685302021-02-09 The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis Mytilineos, Daphne Tsamadou, Chrysanthi Neuchel, Christine Platzbecker, Uwe Bunjes, Donald Schub, Natalie Wagner-Drouet, Eva Wulf, Gerald Kröger, Nicolaus Murawski, Niels Einsele, Hermann Schaefer-Eckart, Kerstin Freitag, Sebastian Casper, Jochen Kaufmann, Martin Dürholt, Mareike Hertenstein, Bernd Klein, Stefan Ringhoffer, Mark Mueller, Carlheinz R. Frank, Sandra Schrezenmeier, Hubert Fuerst, Daniel Mytilineos, Joannis Front Immunol Immunology 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. Frontiers Media S.A. 2021-01-25 /pmc/articles/PMC7868530/ /pubmed/33569061 http://dx.doi.org/10.3389/fimmu.2020.614976 Text en 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 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Mytilineos, Daphne
Tsamadou, Chrysanthi
Neuchel, Christine
Platzbecker, Uwe
Bunjes, Donald
Schub, Natalie
Wagner-Drouet, Eva
Wulf, Gerald
Kröger, Nicolaus
Murawski, Niels
Einsele, Hermann
Schaefer-Eckart, Kerstin
Freitag, Sebastian
Casper, Jochen
Kaufmann, Martin
Dürholt, Mareike
Hertenstein, Bernd
Klein, Stefan
Ringhoffer, Mark
Mueller, Carlheinz R.
Frank, Sandra
Schrezenmeier, Hubert
Fuerst, Daniel
Mytilineos, Joannis
The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis
title The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis
title_full The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis
title_fullStr The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis
title_full_unstemmed The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis
title_short The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis
title_sort human leukocyte antigen-dpb1 degree of compatibility is determined by its expression level and mismatch permissiveness: a german multicenter analysis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868530/
https://www.ncbi.nlm.nih.gov/pubmed/33569061
http://dx.doi.org/10.3389/fimmu.2020.614976
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