Patterns of dendritic cell and monocyte subsets are associated with disease severity and mortality in liver cirrhosis patients

Abstract

Liver cirrhosis is often complicated by an immunological imbalance known as cirrhosis-associated immune dysfunction. This study aimed to investigate disturbances in circulating monocytes and dendritic cells in patients with acute decompensation (AD) of cirrhosis. The sample included 39 adult cirrhotic patients hospitalized for AD, 29 patients with stable cirrhosis (SC), and 30 healthy controls (CTR). Flow cytometry was used to analyze monocyte and dendritic cell subsets in whole blood and quantify cytokines in plasma samples. Cirrhotic groups showed higher frequencies of intermediate monocytes (iMo) than CTR. AD patients had lower percentages of nonclassical monocytes than CTR and SC. Cirrhotic patients had a profound reduction in absolute and relative dendritic cell numbers compared with CTR and showed higher plasmacytoid/classical dendritic cell ratios. Increased plasma levels of IL-6, IL-10, and IL-17A, elevated percentages of CD62L+ monocytes, and reduced HLA-DR expression on classical monocytes (cMo) were also observed in cirrhotic patients. Patients with more advanced liver disease showed increased cMo and reduced tissue macrophages (TiMas) frequencies. It was found that cMo percentages greater than 90.0% within the monocyte compartment and iMo and TiMas percentages lower than 5.7% and 8.6%, respectively, were associated with increased 90-day mortality. Monocytes and dendritic cells are deeply altered in cirrhotic patients, and subset profiles differ between stable and advanced liver disease. High cMo and low TiMas frequencies may be useful biomarkers of disease severity and mortality in liver cirrhosis.

Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression

“…In cirrhotic patients, [130], Cardoso et al observed an increase in circulating intermediate monocytes (CD14 + CD16 + ), distinguished from the classical monocytes (CD14 ++ CD16 − ) and from nonclassical monocytes (CD14 −/low CD16 + ) [131]. They detected alterations in the proportions of circulating monocytes, particularly in patients with more advanced liver disease.…”

Distinct hepatic immunological patterns are associated with the progression or inhibition of hepatocellular carcinoma

“…This is consistent with emerging data demonstrating that imbalance of Th cells promotes NAFLD and chronic liver diseases (He et al, 2017;Zhang et al, 2021). A very recent report demonstrated that patterns of dendritic cells and monocyte subsets are associated with the severity and mortality of patients with liver cirrhosis (Cardoso et al, 2021). In fact, an equilibrium Th1 = Th17 = Th2, NKT = NK, M1 = M2 pattern; semi-equilibrium Th1 = Th17 > Th2, CD8 + = CD4 + , NKT = NK pattern; or predominant CD8 + > CD4 + , Th1 > Th17 > Th2, NKT > NK, M1 > M2 pattern could each exhibit distinctively collective functions independent from the cellular components.…”

The relationship between peripheral immune response and disease severity in SARS‐CoV‐2‐infected subjects: A cross‐sectional study

“…For flow cytometry immunophenotyping, the monoclonal antibodies CD62L (FITC, LT‐TD180), CD4 (PerCP, MEM‐241), and CD11c (PerCP Cy5‐5, BU15) from Exbio; CD10 (PECy7, HI10A), CD3 (APCH7, SK7), CD16 (FITC, 3G8), CD19 (APCH7, HIB19), CD20 (APCH7, 2H7), CD45 (PacO, HI30) and HLA‐DR (PacB, L243) from BD Biosciences; and CD56 (PE, N901 NKH‐1), CD14 (APC, RMO52), and CD123 (PE, SSDCLY107D2) from Beckman Coulter were used. Staining was based on an eight‐colour panel, as previously described by Cardoso and Santos‐Silva (2019) for the identification of monocytes, neutrophils and DCs [ 22 , 23 ]. The expression of CD56 on monocytes and CD62L on monocytes and neutrophils was determined using different panels, which also had markers for these cell lines (HLA‐DR, CD4 and CD45) [ 23 ].…”