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Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure
INTRODUCTION: Acute-on-chronic liver failure (ACLF) is characterized by high levels of systemic inflammation and parallel suppression of innate immunity, whereas little is known about adaptive immune immunity in ACLF. We therefore aimed to characterize the development of the adaptive immune system d...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870861/ https://www.ncbi.nlm.nih.gov/pubmed/33574809 http://dx.doi.org/10.3389/fimmu.2020.534731 |
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author | Rueschenbaum, Sabrina Ciesek, Sandra Queck, Alexander Widera, Marek Schwarzkopf, Katharina Brüne, Bernhard Welsch, Christoph Wedemeyer, Heiner Zeuzem, Stefan Weigert, Andreas Lange, Christian M. |
author_facet | Rueschenbaum, Sabrina Ciesek, Sandra Queck, Alexander Widera, Marek Schwarzkopf, Katharina Brüne, Bernhard Welsch, Christoph Wedemeyer, Heiner Zeuzem, Stefan Weigert, Andreas Lange, Christian M. |
author_sort | Rueschenbaum, Sabrina |
collection | PubMed |
description | INTRODUCTION: Acute-on-chronic liver failure (ACLF) is characterized by high levels of systemic inflammation and parallel suppression of innate immunity, whereas little is known about adaptive immune immunity in ACLF. We therefore aimed to characterize the development of the adaptive immune system during the progression of liver cirrhosis to ACLF. Patients with compensated/stable decompensated liver cirrhosis, acute decompensation of liver cirrhosis, or ACLF were recruited from a prospective cohort study. Comprehensive immunophenotyping was performed using high dimensional flow cytometry. Replication of Torque teno (TT) virus was quantified as a marker of immunosuppression. High frequencies of detectable TT virus were observed already in patients with compensated/stable decompensated liver cirrhosis compared to healthy controls (>50% vs. 19%), suggesting relatively early occurrence of immunosuppression in cirrhosis. In line, profoundly reduced numbers of distinct innate and adaptive immune cell populations were observed before ACLF development. These changes were accompanied by parallel upregulation of co-stimulatory (e.g. CD40L, OX40, CD69, GITR, TIM-1) and inhibitory immune checkpoints (e.g. PDPN, PROCR, 2B4, TIGIT) on CD4+ and CD8+ T cells, which again preceded the development of ACLF. On a functional basis, the capacity of CD4+ and CD8+ T cells to produce pro-inflammatory cytokines upon stimulation was strongly diminished in patients with acute decompensation of liver cirrhosis and ACLF. CONCLUSION: Impaired innate and—in particular—adaptive cellular immunity occurs relatively early in the pathogenesis of liver cirrhosis and precedes ACLF. This may contribute to the development of ACLF by increasing the risk of infections in patients with liver cirrhosis. |
format | Online Article Text |
id | pubmed-7870861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78708612021-02-10 Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure Rueschenbaum, Sabrina Ciesek, Sandra Queck, Alexander Widera, Marek Schwarzkopf, Katharina Brüne, Bernhard Welsch, Christoph Wedemeyer, Heiner Zeuzem, Stefan Weigert, Andreas Lange, Christian M. Front Immunol Immunology INTRODUCTION: Acute-on-chronic liver failure (ACLF) is characterized by high levels of systemic inflammation and parallel suppression of innate immunity, whereas little is known about adaptive immune immunity in ACLF. We therefore aimed to characterize the development of the adaptive immune system during the progression of liver cirrhosis to ACLF. Patients with compensated/stable decompensated liver cirrhosis, acute decompensation of liver cirrhosis, or ACLF were recruited from a prospective cohort study. Comprehensive immunophenotyping was performed using high dimensional flow cytometry. Replication of Torque teno (TT) virus was quantified as a marker of immunosuppression. High frequencies of detectable TT virus were observed already in patients with compensated/stable decompensated liver cirrhosis compared to healthy controls (>50% vs. 19%), suggesting relatively early occurrence of immunosuppression in cirrhosis. In line, profoundly reduced numbers of distinct innate and adaptive immune cell populations were observed before ACLF development. These changes were accompanied by parallel upregulation of co-stimulatory (e.g. CD40L, OX40, CD69, GITR, TIM-1) and inhibitory immune checkpoints (e.g. PDPN, PROCR, 2B4, TIGIT) on CD4+ and CD8+ T cells, which again preceded the development of ACLF. On a functional basis, the capacity of CD4+ and CD8+ T cells to produce pro-inflammatory cytokines upon stimulation was strongly diminished in patients with acute decompensation of liver cirrhosis and ACLF. CONCLUSION: Impaired innate and—in particular—adaptive cellular immunity occurs relatively early in the pathogenesis of liver cirrhosis and precedes ACLF. This may contribute to the development of ACLF by increasing the risk of infections in patients with liver cirrhosis. Frontiers Media S.A. 2021-01-26 /pmc/articles/PMC7870861/ /pubmed/33574809 http://dx.doi.org/10.3389/fimmu.2020.534731 Text en Copyright © 2021 Rueschenbaum, Ciesek, Queck, Widera, Schwarzkopf, Brüne, Welsch, Wedemeyer, Zeuzem, Weigert and Lange http://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 Rueschenbaum, Sabrina Ciesek, Sandra Queck, Alexander Widera, Marek Schwarzkopf, Katharina Brüne, Bernhard Welsch, Christoph Wedemeyer, Heiner Zeuzem, Stefan Weigert, Andreas Lange, Christian M. Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure |
title | Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure |
title_full | Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure |
title_fullStr | Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure |
title_full_unstemmed | Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure |
title_short | Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure |
title_sort | dysregulated adaptive immunity is an early event in liver cirrhosis preceding acute-on-chronic liver failure |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870861/ https://www.ncbi.nlm.nih.gov/pubmed/33574809 http://dx.doi.org/10.3389/fimmu.2020.534731 |
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