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

• Main Authors: Emmanuel Weiss, Pierre de la Grange, Mylène Defaye, Juan José Lozano, Ferrán Aguilar, Pushpa Hegde, Ariane Jolly, Lucile Moga, Sukriti Sukriti, Banwari Agarwal, Haqeeqat Gurm, Marion Tanguy, Johanne Poisson, Joan Clària, Paer-Selim Abback, Axel Périanin, Gautam Mehta, Rajiv Jalan, Claire Francoz, Pierre-Emmanuel Rautou, Sophie Lotersztajn, Vicente Arroyo, François Durand, Richard Moreau
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-02-01
• Series: Frontiers in Immunology
• Subjects: myeloid cells; innate lymphoid cells; adaptive immune cells; sepsis; organ failure; immunotherapies
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2020.619039/full

Background and AimsPatients 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 MethodsBlood 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.ResultsSeveral 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.ConclusionsGenomic 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.