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, Jahrgang 11, 614976, 2020.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -