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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-7868530 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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