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Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings

Despite the critical role of cytokines in allograft rejection, the relation of peripheral blood cytokine profiles to clinical kidney transplant rejection has not been fully elucidated. We assessed 28 cytokines through multiplex assay in 293 blood samples from kidney transplant recipients at time of...

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Autores principales: Van Loon, Elisabet, Lamarthée, Baptiste, Barba, Thomas, Claes, Sandra, Coemans, Maarten, de Loor, Henriette, Emonds, Marie-Paule, Koshy, Priyanka, Kuypers, Dirk, Proost, Paul, Senev, Aleksandar, Sprangers, Ben, Tinel, Claire, Thaunat, Olivier, Van Craenenbroeck, Amaryllis H., Schols, Dominique, Naesens, Maarten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904423/
https://www.ncbi.nlm.nih.gov/pubmed/35281018
http://dx.doi.org/10.3389/fimmu.2022.818569
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author Van Loon, Elisabet
Lamarthée, Baptiste
Barba, Thomas
Claes, Sandra
Coemans, Maarten
de Loor, Henriette
Emonds, Marie-Paule
Koshy, Priyanka
Kuypers, Dirk
Proost, Paul
Senev, Aleksandar
Sprangers, Ben
Tinel, Claire
Thaunat, Olivier
Van Craenenbroeck, Amaryllis H.
Schols, Dominique
Naesens, Maarten
author_facet Van Loon, Elisabet
Lamarthée, Baptiste
Barba, Thomas
Claes, Sandra
Coemans, Maarten
de Loor, Henriette
Emonds, Marie-Paule
Koshy, Priyanka
Kuypers, Dirk
Proost, Paul
Senev, Aleksandar
Sprangers, Ben
Tinel, Claire
Thaunat, Olivier
Van Craenenbroeck, Amaryllis H.
Schols, Dominique
Naesens, Maarten
author_sort Van Loon, Elisabet
collection PubMed
description Despite the critical role of cytokines in allograft rejection, the relation of peripheral blood cytokine profiles to clinical kidney transplant rejection has not been fully elucidated. We assessed 28 cytokines through multiplex assay in 293 blood samples from kidney transplant recipients at time of graft dysfunction. Unsupervised hierarchical clustering identified a subset of patients with increased pro-inflammatory cytokine levels. This patient subset was hallmarked by a high prevalence (75%) of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA) and histological rejection (70%) and had worse graft survival compared to the group with low cytokine levels (HLA-DSA in 1.7% and rejection in 33.7%). Thirty percent of patients with high pro-inflammatory cytokine levels and HLA-DSA did not have histological rejection. Exploring the cellular origin of these cytokines, we found a corresponding expression in endothelial cells, monocytes, and natural killer cells in single-cell RNASeq data from kidney transplant biopsies. Finally, we confirmed secretion of these cytokines in HLA-DSA-mediated cross talk between endothelial cells, NK cells, and monocytes. In conclusion, blood pro-inflammatory cytokines are increased in kidney transplant patients with HLA-DSA, even in the absence of histology of rejection. These observations challenge the concept that histology is the gold standard for identification of ongoing allo-immune activation after transplantation.
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spelling pubmed-89044232022-03-10 Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings Van Loon, Elisabet Lamarthée, Baptiste Barba, Thomas Claes, Sandra Coemans, Maarten de Loor, Henriette Emonds, Marie-Paule Koshy, Priyanka Kuypers, Dirk Proost, Paul Senev, Aleksandar Sprangers, Ben Tinel, Claire Thaunat, Olivier Van Craenenbroeck, Amaryllis H. Schols, Dominique Naesens, Maarten Front Immunol Immunology Despite the critical role of cytokines in allograft rejection, the relation of peripheral blood cytokine profiles to clinical kidney transplant rejection has not been fully elucidated. We assessed 28 cytokines through multiplex assay in 293 blood samples from kidney transplant recipients at time of graft dysfunction. Unsupervised hierarchical clustering identified a subset of patients with increased pro-inflammatory cytokine levels. This patient subset was hallmarked by a high prevalence (75%) of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA) and histological rejection (70%) and had worse graft survival compared to the group with low cytokine levels (HLA-DSA in 1.7% and rejection in 33.7%). Thirty percent of patients with high pro-inflammatory cytokine levels and HLA-DSA did not have histological rejection. Exploring the cellular origin of these cytokines, we found a corresponding expression in endothelial cells, monocytes, and natural killer cells in single-cell RNASeq data from kidney transplant biopsies. Finally, we confirmed secretion of these cytokines in HLA-DSA-mediated cross talk between endothelial cells, NK cells, and monocytes. In conclusion, blood pro-inflammatory cytokines are increased in kidney transplant patients with HLA-DSA, even in the absence of histology of rejection. These observations challenge the concept that histology is the gold standard for identification of ongoing allo-immune activation after transplantation. Frontiers Media S.A. 2022-02-23 /pmc/articles/PMC8904423/ /pubmed/35281018 http://dx.doi.org/10.3389/fimmu.2022.818569 Text en Copyright © 2022 Van Loon, Lamarthée, Barba, Claes, Coemans, de Loor, Emonds, Koshy, Kuypers, Proost, Senev, Sprangers, Tinel, Thaunat, Van Craenenbroeck, Schols and Naesens 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
Van Loon, Elisabet
Lamarthée, Baptiste
Barba, Thomas
Claes, Sandra
Coemans, Maarten
de Loor, Henriette
Emonds, Marie-Paule
Koshy, Priyanka
Kuypers, Dirk
Proost, Paul
Senev, Aleksandar
Sprangers, Ben
Tinel, Claire
Thaunat, Olivier
Van Craenenbroeck, Amaryllis H.
Schols, Dominique
Naesens, Maarten
Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings
title Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings
title_full Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings
title_fullStr Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings
title_full_unstemmed Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings
title_short Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings
title_sort circulating donor-specific anti-hla antibodies associate with immune activation independent of kidney transplant histopathological findings
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904423/
https://www.ncbi.nlm.nih.gov/pubmed/35281018
http://dx.doi.org/10.3389/fimmu.2022.818569
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