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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

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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. / 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.

In: FRONT IMMUNOL, Vol. 11, 614976, 2020.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Mytilineos, D, Tsamadou, C, Neuchel, C, Platzbecker, U, Bunjes, D, Schub, N, Wagner-Drouet, E, Wulf, G, Kröger, N, Murawski, N, Einsele, H, Schaefer-Eckart, K, Freitag, S, Casper, J, Kaufmann, M, Dürholt, M, Hertenstein, B, Klein, S, Ringhoffer, M, Mueller, CR, Frank, S, Schrezenmeier, H, Fuerst, D & Mytilineos, J 2020, 'The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis', FRONT IMMUNOL, vol. 11, 614976. https://doi.org/10.3389/fimmu.2020.614976

APA

Mytilineos, D., Tsamadou, C., Neuchel, C., Platzbecker, U., Bunjes, D., Schub, N., Wagner-Drouet, E., Wulf, G., Kröger, N., Murawski, N., Einsele, H., Schaefer-Eckart, K., Freitag, S., Casper, J., Kaufmann, M., Dürholt, M., Hertenstein, B., Klein, S., Ringhoffer, M., ... Mytilineos, J. (2020). The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis. FRONT IMMUNOL, 11, [614976]. https://doi.org/10.3389/fimmu.2020.614976

Vancouver

Mytilineos D, Tsamadou C, Neuchel C, Platzbecker U, Bunjes D, Schub N et al. The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis. FRONT IMMUNOL. 2020;11. 614976. https://doi.org/10.3389/fimmu.2020.614976

Bibtex

@article{9483cb6ccd6a47cab9ff444640792427,
title = "The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis",
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.",
keywords = "3' Untranslated Regions/genetics, Adolescent, Adult, Aged, Alleles, Allografts, Bone Marrow Transplantation, Child, Child, Preschool, Epitopes, T-Lymphocyte/immunology, Female, Germany, Graft vs Host Disease/epidemiology, Graft vs Leukemia Effect/immunology, HLA-DP beta-Chains/analysis, Histocompatibility, Histocompatibility Testing/methods, Humans, Incidence, Infant, Infant, Newborn, Kaplan-Meier Estimate, Lymphocyte Depletion, Male, Middle Aged, Models, Immunological, Peripheral Blood Stem Cell Transplantation, Polymorphism, Single Nucleotide, Retrospective Studies, Risk, Unrelated Donors, Young Adult",
author = "Daphne Mytilineos and Chrysanthi Tsamadou and Christine Neuchel and Uwe Platzbecker and Donald Bunjes and Natalie Schub and Eva Wagner-Drouet and Gerald Wulf and Nicolaus Kr{\"o}ger and Niels Murawski and Hermann Einsele and Kerstin Schaefer-Eckart and Sebastian Freitag and Jochen Casper and Martin Kaufmann and Mareike D{\"u}rholt and Bernd Hertenstein and Stefan Klein and Mark Ringhoffer and Mueller, {Carlheinz R} and Sandra Frank and Hubert Schrezenmeier and Daniel Fuerst and Joannis Mytilineos",
note = "Copyright {\textcopyright} 2021 Mytilineos, Tsamadou, Neuchel, Platzbecker, Bunjes, Schub, Wagner-Drouet, Wulf, Kr{\"o}ger, Murawski, Einsele, Schaefer-Eckart, Freitag, Casper, Kaufmann, D{\"u}rholt, Hertenstein, Klein, Ringhoffer, Mueller, Frank, Schrezenmeier, Fuerst and Mytilineos.",
year = "2020",
doi = "10.3389/fimmu.2020.614976",
language = "English",
volume = "11",
journal = "FRONT IMMUNOL",
issn = "1664-3224",
publisher = "Lausanne : Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis

AU - Mytilineos, Daphne

AU - Tsamadou, Chrysanthi

AU - Neuchel, Christine

AU - Platzbecker, Uwe

AU - Bunjes, Donald

AU - Schub, Natalie

AU - Wagner-Drouet, Eva

AU - Wulf, Gerald

AU - Kröger, Nicolaus

AU - Murawski, Niels

AU - Einsele, Hermann

AU - Schaefer-Eckart, Kerstin

AU - Freitag, Sebastian

AU - Casper, Jochen

AU - Kaufmann, Martin

AU - Dürholt, Mareike

AU - Hertenstein, Bernd

AU - Klein, Stefan

AU - Ringhoffer, Mark

AU - Mueller, Carlheinz R

AU - Frank, Sandra

AU - Schrezenmeier, Hubert

AU - Fuerst, Daniel

AU - Mytilineos, Joannis

N1 - 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.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - 3' Untranslated Regions/genetics

KW - Adolescent

KW - Adult

KW - Aged

KW - Alleles

KW - Allografts

KW - Bone Marrow Transplantation

KW - Child

KW - Child, Preschool

KW - Epitopes, T-Lymphocyte/immunology

KW - Female

KW - Germany

KW - Graft vs Host Disease/epidemiology

KW - Graft vs Leukemia Effect/immunology

KW - HLA-DP beta-Chains/analysis

KW - Histocompatibility

KW - Histocompatibility Testing/methods

KW - Humans

KW - Incidence

KW - Infant

KW - Infant, Newborn

KW - Kaplan-Meier Estimate

KW - Lymphocyte Depletion

KW - Male

KW - Middle Aged

KW - Models, Immunological

KW - Peripheral Blood Stem Cell Transplantation

KW - Polymorphism, Single Nucleotide

KW - Retrospective Studies

KW - Risk

KW - Unrelated Donors

KW - Young Adult

U2 - 10.3389/fimmu.2020.614976

DO - 10.3389/fimmu.2020.614976

M3 - SCORING: Journal article

C2 - 33569061

VL - 11

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

M1 - 614976

ER -