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ORIGINAL RESEARCH article

Front. Genet.
Sec. Immunogenetics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1436194
This article is part of the Research Topic Novel Applications of Epitope Biology to Improve Outcomes in Transplantation View all 4 articles

Allogeneic mesenchymal stromal cell therapy in kidney transplantation: should repeated HLA mismatches be avoided?

Provisionally accepted
Suzanne Bezstarosti Suzanne Bezstarosti 1,2*Pauline Erpicum Pauline Erpicum 3,4Gianni Maggipinto Gianni Maggipinto 5Geertje Dreyer Geertje Dreyer 2Marlies Reinders Marlies Reinders 2Soufian Meziyerh Soufian Meziyerh 2Dave Roelen Dave Roelen 1Johan W. De Fijter Johan W. De Fijter 2Jesper Kers Jesper Kers 6Laurent E. Weekers Laurent E. Weekers 4Yves Beguin Yves Beguin 7François Jouret François Jouret 3,4Sebastiaan Heidt Sebastiaan Heidt 1*
  • 1 Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
  • 2 Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, Netherlands
  • 3 University of Liège, Liège, Belgium
  • 4 Department of Nephrology, University Hospital of Liège, Liege, Liège, Belgium
  • 5 University Hospital of Liège, Liège, Belgium
  • 6 Department of Pathology, Leiden University Medical Center (LUMC), Leiden, Netherlands
  • 7 Department of Clinical Hematology, University Hospital of Liège, Liège, Belgium

The final, formatted version of the article will be published soon.

    Mesenchymal stromal cells (MSC) have immunomodulatory properties and are therefore a promising tool in kidney transplantation. While most studies have been conducted with autologous MSC, using allogeneic MSC as an off-the-shelve product is more feasible in clinical settings. However, allogeneic MSC could potentially induce an immune response, which might eventually be directed towards the kidney allograft, because of shared HLA epitope mismatches between the kidney and MSC donor. In this study, we performed in-depth analysis of two cohorts (n=20) that received third-party MSC therapy after kidney transplantation. While the Neptune Study from Leiden University Medical Center specifically selected MSC to avoid repeated HLA antigen mismatches between kidney and MSC donors, the study from the University of Liège did not perform specific MSC selection. The comparative analysis of amino acid mismatches between these cohorts showed that selection of MSC to avoid repeated HLA mismatches at the split antigen level is not sufficient to prevent repeated mismatches at the amino acid level. However, repeated amino acid mismatches were not associated with the occurrence of donor-specific antibodies (DSA). The clinical relevance of repeated amino acid mismatches seems therefore limited for the risk of DSA formation. Since DSA formation in this study was limited (3 of 20 patients), larger studies are required to confirm that it is not necessary to prevent repeated HLA mismatches in allogeneic MSC therapy in kidney transplantation.

    Keywords: Mesenchymal stromal cells (MSC), human leukocyte antigen (HLA), kidney transplanation, epitope, eplet, Donor specific antibodies, Amino acid, mismatch

    Received: 21 May 2024; Accepted: 15 Aug 2024.

    Copyright: © 2024 Bezstarosti, Erpicum, Maggipinto, Dreyer, Reinders, Meziyerh, Roelen, De Fijter, Kers, Weekers, Beguin, Jouret and Heidt. 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) or licensor 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.

    * Correspondence:
    Suzanne Bezstarosti, Department of Immunology, Leiden University Medical Center (LUMC), Leiden, 2300 RC, Netherlands
    Sebastiaan Heidt, Department of Immunology, Leiden University Medical Center (LUMC), Leiden, 2300 RC, Netherlands

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.