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

Mytilineos D, Tsamadou C, Neuchel C, Platzbecker U, Bunjes D, Schub N, Wagner-Drouet E, Wulf G, Kroger N, Murawski N, Einsele H, Schaefer-Eckart K, Freitag S, Casper J, Kaufmann M, Duerholt M, Hertenstein B, Klein S, Ringhoffer M, Mueller CR, Frank S, Schrezenmeier H, Fuerst D, Mytilineos J (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 11

Article Number: 614976

DOI: 10.3389/fimmu.2020.614976

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.

Involved external institutions

DRK-Blutspendedienst Baden-Württemberg - Hessen / German Red Cross Blood Donor Service Baden-Wuerttemberg – Hessen Germany (DE) Universitätsklinikum Würzburg Germany (DE) Deutsches Register für Stammzelltransplantationen e.V. (DRST) Germany (DE) Universität Leipzig Germany (DE) Universität Ulm Germany (DE) Christian-Albrechts-Universität zu Kiel Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) Germany (DE) Georg-August-Universität Göttingen Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Klinikum Nürnberg Germany (DE) Universität Rostock Germany (DE) Carl von Ossietzky Universität Oldenburg Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) Elisabeth-Krankenhaus Essen Germany (DE) Klinikverbund Bremen (Gesundheit Nord) Germany (DE) Universitätsklinikum Mannheim Germany (DE) Städtisches Klinikum Karlsruhe Germany (DE) Zentrales Knochenmarkspender-Register für die Bundesrepublik Deutschland gGmbH (ZKRD) Germany (DE)

How to cite

APA:

Mytilineos, D., Tsamadou, C., Neuchel, C., Platzbecker, U., Bunjes, D., Schub, N.,... Mytilineos, J. (2021). The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.614976

MLA:

Mytilineos, Daphne, et al. "The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis." Frontiers in Immunology 11 (2021).

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