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Your search keyword '"Suzanne Bezstarosti"' showing total 4 results
Start Over Author "Suzanne Bezstarosti" Topic genetics
4 results on '"Suzanne Bezstarosti"'

1. Allogeneic mesenchymal stromal cell therapy in kidney transplantation: should repeated human leukocyte antigen mismatches be avoided?

Author

Suzanne Bezstarosti, Pauline Erpicum, Gianni Maggipinto, Geertje J. Dreyer, Marlies E. J. Reinders, Soufian Meziyerh, Dave L. Roelen, Johan W. De Fijter, Jesper Kers, Laurent Weekers, Yves Beguin, François Jouret, and Sebastiaan Heidt

Subjects
mesenchymal stromal cells, human leukocyte antigen, kidney transplantation, epitope, eplet, donor-specific antibodies, Genetics, QH426-470
Abstract

Mesenchymal stromal cells (MSCs) have immunomodulatory properties and are therefore considered promising tools in kidney transplantation. Although most studies have been conducted with autologous MSCs, using allogeneic MSCs as an off-the-shelf product is more feasible in clinical settings. However, allogeneic MSCs could potentially induce an immune response, which might eventually be directed towards the kidney allograft because of shared human leukocyte antigen (HLA) epitope mismatches between the kidney and MSC donor. In this study, we performed in-depth analyses 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 analyses of amino acid mismatches between these cohorts showed that MSC selection to avoid repeated HLA mismatches at the split antigen level was 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 (DSAs). Thus, the clinical relevance of repeated amino acid mismatches seems to be limited with regard to the risk of DSA formation. Since DSA formation was limited (3 of 20 patients) in this study, larger studies are required to investigate the relevance of preventing repeated HLA mismatches in allogeneic MSC therapy in kidney transplantation.

Published
2024
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2. <scp>HLA</scp> antibody affinity determination: From <scp>HLA</scp> ‐specific monoclonal antibodies to donor <scp>HLA</scp> specific antibodies ( <scp>DSA</scp> ) in patient serum

Author

Melanie N. Hug, Sabrina Keller, Talea Marty, Daniel Gygax, Dominik Meinel, Peter Spies, Joëlle Handschin, Marc Kleiser, Noemi Vazquez, Janina Linnik, Rico Buchli, Frans Claas, Sebastiaan Heidt, Cynthia S. M. Kramer, Suzanne Bezstarosti, Jar‐How Lee, Stefan Schaub, and Gideon Hönger

Subjects
Immunology, Genetics, Immunology and Allergy
Published
2023
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3. HLA-DQ eplet mismatch load may identify kidney transplant patients eligible for tacrolimus withdrawal without donor-specific antibody formation after mesenchymal stromal cell therapy

Author

Suzanne Bezstarosti, Soufian Meziyerh, Marlies E. J. Reinders, Kim Voogt‐Bakker, Koen E. Groeneweg, Dave L. Roelen, Jesper Kers, Johan W. de Fijter, Sebastiaan Heidt, Pathology, AII - Inflammatory diseases, APH - Digital Health, and APH - Global Health

Subjects
HLA, Immunology, eplet, mesenchymal stromal cell, Genetics, HLA-DQ, Immunology and Allergy, tacrolimus, donor-specific antibodies, transplantation
Abstract

Recently, the randomized phase-II Triton study demonstrated that mesenchymal stromal cell (MSC) therapy facilitated early tacrolimus withdrawal in living donor kidney transplant recipients. The current sub-study analyzed formation of de novo donor-specific HLA antibodies (dnDSA) in the context of the degree of HLA eplet mismatches. At the time of protocol biopsy at 6 months, 7/29 patients (24%) in the MSC group and 1/27 patient (3.7%) in the control group had developed dnDSA. In the MSC group, all dnDSA were anti-HLA-DQ; two patients had anti-DQ alone and five patients combined with anti-class I, HLA-DR or -DP. Despite excess dnDSA formation in the MSC-arm of the study, the evolution of eGFR (CKD-EPI) and proteinuria were comparable 2 years posttransplant. All dnDSA were complement-binding and three patients had antibody-mediated rejection in the protocol biopsy, but overall rejection episodes were not increased. Everolimus had to be discontinued in nine patients because of toxicity, and tacrolimus was reintroduced in six patients because of dnDSA formation. The HLA-DQ eplet mismatch load independently associated with dnDSA (adjusted hazard ratio = 1.07 per eplet mismatch, p = 0.008). A threshold of ≥11 HLA-DQ eplet mismatches predicted subsequent dnDSA in all 11 patients in the MSC group, but specificity was low (44%). Further research is warranted to explore HLA molecular mismatch load as a biomarker to guide personalized maintenance immunosuppression in kidney transplantation.

Published
2023

4. Site-directed mutagenesis of HLA molecules reveals the functional epitope of a human HLA-A1/A36-specific monoclonal antibody

Author

Tina Meng, Suzanne Bezstarosti, Ujjwala Singh, Michelle Yap, Laura Scott, Naiiry Petrosyan, Fred Quiroz, Ned Van Eps, Eric Ka‐Wai Hui, David Suh, Quansheng Zhu, Rui Pei, Cynthia S. M. Kramer, Frans H. J. Claas, David Lowe, and Sebastiaan Heidt

Subjects
monoclonal antibody, Immunology, antigenicity, eplet, Genetics, Immunology and Allergy, antibody verification, immunogenicity, reactivity pattern, site-directed mutagenesis
Abstract

Eplet 44KM is currently listed in the HLA Epitope Registry but does not adhere to the eplet definition of an amino acid configuration within a 3.5 angstrom radius. Eplet 44KM has been previously redefined to the antibody-verified reactivity pattern 44K/150V/158V, based on reactivity analysis of monoclonal antibody VDK1D12. Since the three residues are always simultaneously present on common HLA alleles, methods to define which residue is crucial for antibody-induction and binding are limited. In this proof-of-concept study, we performed site-directed mutagenesis to narrow down the antibody-verified reactivity pattern 44K/150V/158V to a single amino acid and defined 44K as the eplet or functional epitope of mAb VDK1D12.

Published
2022

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