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Elevated soluble human leukocyte antigen G levels in patients after allogeneic stem cell transplantation are associated with less severe acute and chronic graft-versus-host disease

Bone Marrow Transplantation volume 53, pages 1149–1156 (2018)Cite this article

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Abstract

HLA-G is a non-classical class I molecule which induces tolerance in allogeneic situations by inhibition of cytotoxic NK and CD8 + T cells and by induction of regulatory T cells. Concordantly, in solid organ transplantation HLA-G is associated with a lower risk for acute and chronic rejection, whereas its role in allogeneic stem cell transplantation (allo-SCT) is less established. We here present detailed analyses of HLA-G-levels in patients after allo-SCT showing a correlation of elevated soluble HLA-G (sHLA-G) levels with less severe acute (p = 0.06) and chronic GvHD (p = 0.0025) and with a superior overall survival (p = 0.03). Soluble HLA-G levels are also positively correlated with the frequency of regulatory T cells in vivo. These clinical data are corroborated by in vitro analyses showing that patients-derived sHLA-G inhibit allogeneic immune responses. ATG-treatment of patients dominantly affects the sHLA-G levels post allo-SCT. Thus, this study highlights the association of elevated sHLA-G levels with less severe acute and chronic GvHD and provides additional functional analyses elucidating possible tolerance-inducing mechanisms of sHLA-G in the context of allo-SCT.

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Acknowledgements

This study was supported by the Deutsche José Carreras Leukämie-Stiftung e.V. (DJCLS R 07/06 v). Special thanks go to the patients and donors providing the blood samples for this study. We are grateful for the technical support of Sabine Schramm, Monika Collenburg, Ines Krimphoff, Ursel Hill, and Martina Franke as well as other members of the team of the Institute for Transfusion Medicine and the colleagues from the department of Bone Marrow Transplantation, all University Hospital Essen.

Author contributions

VR and LK conceived, designed and performed the experiments, analyzed the data and wrote the manuscript. FSN, BW, MD, TL, ML, FMH, PAH, and DWB confirmed the analyses and assisted in correcting the manuscript.

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Authors and Affiliations

  1. Department of Bone Marrow Transplantation, University Hospital Essen, Essen, 45147, Germany

    Lambros Kordelas, Markus Ditschkowski, Tobias Liebregts & Dietrich W. Beelen

  2. Institute for Transfusion Medicine, University Hospital Essen, Essen, 45147, Germany

    Fabiola da Silva Nardi, Bettina Wagner, Monika Lindemann, Falko M. Heinemann, Peter A. Horn & Vera Rebmann

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  1. Lambros Kordelas
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Correspondence to Lambros Kordelas.

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Kordelas, L., da Silva Nardi, F., Wagner, B. et al. Elevated soluble human leukocyte antigen G levels in patients after allogeneic stem cell transplantation are associated with less severe acute and chronic graft-versus-host disease. Bone Marrow Transplant 53, 1149–1156 (2018). https://doi.org/10.1038/s41409-018-0145-1

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