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Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF

Weiss, E; de la Grange, P; Defaye, M; Jose Lozano, J; Aguilar, F; Hegde, P; Jolly, A; ... Moreau, R; + view all (2021) Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF. Frontiers in Immunology , 11 , Article 619039. 10.3389/fimmu.2020.619039. Green open access

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Abstract

BACKGROUND AND AIMS: Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets in these patients. MATERIAL AND METHODS: Blood taken from 67 patients with decompensated cirrhosis (including 35 critically ill with ACLF in the intensive care unit), and 12 healthy subjects, was assigned to either measurements of clinical blood counts and microarray (genomewide) analysis of RNA expression in whole-blood; microarray (genomewide) analysis of RNA expression in blood neutrophils; or assessment of neutrophil antimicrobial functions. RESULTS: Several features were found in patients with ACLF and not in those without ACLF. Indeed, clinical blood count measurements showed that patients with ACLF were characterized by leukocytosis, neutrophilia, and lymphopenia. Using the CIBERSORT method to deconvolute the whole-blood RNA-expression data, revealed that the hallmark of ACLF was the association of neutrophilia with increased proportions of macrophages M0-like monocytes and decreased proportions of memory lymphocytes (of B-cell, CD4 T-cell lineages), CD8 T cells and natural killer cells. Microarray analysis of neutrophil RNA expression revealed that neutrophils from patients with ACLF had a unique phenotype including induction of glycolysis and granule genes, and downregulation of cell-migration and cell-cycle genes. Moreover, neutrophils from these patients had defective production of the antimicrobial superoxide anion. CONCLUSIONS: Genomic analysis revealed that, among patients with decompensated cirrhosis, those with ACLF were characterized by dysregulation of blood immune cells, including increases in neutrophils (that had a unique phenotype) and macrophages M0-like monocytes, and depletion of several lymphocyte subsets (including memory lymphocytes). All these lymphocyte alterations, along with defective neutrophil superoxide anion production, may contribute to immunosuppression in ACLF, suggesting targets for future therapies.

Type: Article
Title: Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2020.619039
Publisher version: https://doi.org/10.3389/fimmu.2020.619039
Language: English
Additional information: © 2021 Weiss, de la Grange, Defaye, Lozano, Aguilar, Hegde, Jolly, Moga, Sukriti, Agarwal, Gurm, Tanguy, Poisson, Clària, Abback, Périanin, Mehta, Jalan, Francoz, Rautou, Lotersztajn, Arroyo, Durand and Moreau. 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.
Keywords: Myeloid cells, innate lymphoid cells, adaptive immune cells, sepsis, organ failure, immunotherapies
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/10124153
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