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Renal Endothelial Cytotoxicity Assay to Diagnose and Monitor Renal Transplant Recipients for Anti-Endothelial Antibodies

Tissue-specific nonhuman leukocyte antigen (HLA) antigens can play crucial roles in allograft immunity and have been shown to trigger humoral responses leading to rejection of HLA-matched kidney allografts. Interest in the role of endothelial-specific antigens has grown over the past years, and seve...

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Autores principales: Lammerts, Rosa G. M., van den Born, Jacob, Huberts-Kregel, Magdalena, Gomes-Neto, Antonio W., Daha, Mohammed R., Hepkema, Bouke G., Sanders, Jan-Stephan, Pol, Robert A., Diepstra, Arjan, Berger, Stefan P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207246/
https://www.ncbi.nlm.nih.gov/pubmed/35734182
http://dx.doi.org/10.3389/fimmu.2022.845187
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author Lammerts, Rosa G. M.
van den Born, Jacob
Huberts-Kregel, Magdalena
Gomes-Neto, Antonio W.
Daha, Mohammed R.
Hepkema, Bouke G.
Sanders, Jan-Stephan
Pol, Robert A.
Diepstra, Arjan
Berger, Stefan P.
author_facet Lammerts, Rosa G. M.
van den Born, Jacob
Huberts-Kregel, Magdalena
Gomes-Neto, Antonio W.
Daha, Mohammed R.
Hepkema, Bouke G.
Sanders, Jan-Stephan
Pol, Robert A.
Diepstra, Arjan
Berger, Stefan P.
author_sort Lammerts, Rosa G. M.
collection PubMed
description Tissue-specific nonhuman leukocyte antigen (HLA) antigens can play crucial roles in allograft immunity and have been shown to trigger humoral responses leading to rejection of HLA-matched kidney allografts. Interest in the role of endothelial-specific antigens has grown over the past years, and several case reports have been described in which antibodies reacting with endothelial cells (ECs) are associated with rejection. Such antibodies escape the detection in conventional crossmatch tests as they do not react with lymphocytes. However, due to the heterogeneity of endothelial cells from different vascular beds, it remains difficult to draw organ-specific conclusions from studies describing endothelial crossmatch assays. We present a case of a 69-year-old male patient whose kidney allograft was rejected as hyperacute, despite the absence of pretransplant HLA-specific antibodies. To place findings from previous studies in a kidney-related context, we performed crossmatch assays with primary renal endothelial cells. The patient’s serum was reactive with primary renal ECs, demonstrated by antibody binding and complement-dependent cytotoxicity. Antibodies from this patient did not react with lymphocytes nor were HLA donor-specific antibodies (DSAs) found. Two years later, the patient successfully received a second kidney transplant after treatment with rituximab and plasmapheresis before and after transplantation. We demonstrated that the removal of antibodies against non-HLA EC-specific molecules can be monitored using a primary renal EC crossmatch test, possibly contributing to a successful transplantation outcome.
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spelling pubmed-92072462022-06-21 Renal Endothelial Cytotoxicity Assay to Diagnose and Monitor Renal Transplant Recipients for Anti-Endothelial Antibodies Lammerts, Rosa G. M. van den Born, Jacob Huberts-Kregel, Magdalena Gomes-Neto, Antonio W. Daha, Mohammed R. Hepkema, Bouke G. Sanders, Jan-Stephan Pol, Robert A. Diepstra, Arjan Berger, Stefan P. Front Immunol Immunology Tissue-specific nonhuman leukocyte antigen (HLA) antigens can play crucial roles in allograft immunity and have been shown to trigger humoral responses leading to rejection of HLA-matched kidney allografts. Interest in the role of endothelial-specific antigens has grown over the past years, and several case reports have been described in which antibodies reacting with endothelial cells (ECs) are associated with rejection. Such antibodies escape the detection in conventional crossmatch tests as they do not react with lymphocytes. However, due to the heterogeneity of endothelial cells from different vascular beds, it remains difficult to draw organ-specific conclusions from studies describing endothelial crossmatch assays. We present a case of a 69-year-old male patient whose kidney allograft was rejected as hyperacute, despite the absence of pretransplant HLA-specific antibodies. To place findings from previous studies in a kidney-related context, we performed crossmatch assays with primary renal endothelial cells. The patient’s serum was reactive with primary renal ECs, demonstrated by antibody binding and complement-dependent cytotoxicity. Antibodies from this patient did not react with lymphocytes nor were HLA donor-specific antibodies (DSAs) found. Two years later, the patient successfully received a second kidney transplant after treatment with rituximab and plasmapheresis before and after transplantation. We demonstrated that the removal of antibodies against non-HLA EC-specific molecules can be monitored using a primary renal EC crossmatch test, possibly contributing to a successful transplantation outcome. Frontiers Media S.A. 2022-06-06 /pmc/articles/PMC9207246/ /pubmed/35734182 http://dx.doi.org/10.3389/fimmu.2022.845187 Text en Copyright © 2022 Lammerts, Born, Huberts-Kregel, Gomes-Neto, Daha, Hepkema, Sanders, Pol, Diepstra and Berger https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Immunology
Lammerts, Rosa G. M.
van den Born, Jacob
Huberts-Kregel, Magdalena
Gomes-Neto, Antonio W.
Daha, Mohammed R.
Hepkema, Bouke G.
Sanders, Jan-Stephan
Pol, Robert A.
Diepstra, Arjan
Berger, Stefan P.
Renal Endothelial Cytotoxicity Assay to Diagnose and Monitor Renal Transplant Recipients for Anti-Endothelial Antibodies
title Renal Endothelial Cytotoxicity Assay to Diagnose and Monitor Renal Transplant Recipients for Anti-Endothelial Antibodies
title_full Renal Endothelial Cytotoxicity Assay to Diagnose and Monitor Renal Transplant Recipients for Anti-Endothelial Antibodies
title_fullStr Renal Endothelial Cytotoxicity Assay to Diagnose and Monitor Renal Transplant Recipients for Anti-Endothelial Antibodies
title_full_unstemmed Renal Endothelial Cytotoxicity Assay to Diagnose and Monitor Renal Transplant Recipients for Anti-Endothelial Antibodies
title_short Renal Endothelial Cytotoxicity Assay to Diagnose and Monitor Renal Transplant Recipients for Anti-Endothelial Antibodies
title_sort renal endothelial cytotoxicity assay to diagnose and monitor renal transplant recipients for anti-endothelial antibodies
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207246/
https://www.ncbi.nlm.nih.gov/pubmed/35734182
http://dx.doi.org/10.3389/fimmu.2022.845187
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