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Published on: September 11, 2019
Hepatitis C patients on maintenance hemodialysis show complex immune disturbances in the peripheral blood
Masaaki Shiina1, Koju Kobayashi, Kazumasa Hiroishi
11 Department of Gastroenterology and Hepatology, Shin-Yurigaoka General Hospital , Kawasaki, Japan .
Insights
Hepatitis C virus (HCV) infection impairs innate immunity in hemodialysis patients. Chronic HCV affects natural killer cells and monocytes, independent of hemodialysis, impacting patient survival.
Area of Science:
- Immunology
- Virology
- Nephrology
Background:
- Hepatitis C virus (HCV) infection is common in hemodialysis (HD) patients, affecting survival.
- Both HCV and HD are associated with impaired innate immunity.
- Antiviral treatment options for HCV in HD patients are limited.
Purpose of the Study:
- To compare peripheral immunologic features in patients with maintenance hemodialysis and/or HCV infection.
- To investigate the impact of chronic HCV infection on innate immunity in the context of hemodialysis.
Main Methods:
- Analysis of peripheral blood mononuclear cells (PBMCs) from 30 subjects in four groups (HD, HCV, HD+HCV, controls).
- Flow cytometry to analyze Natural Killer (NK) cell subsets and activation status (CD69 expression).
- Cytokine production (Interferon-gamma, Tumor Necrosis Factor-alpha) measured via culture supernatant and single-cell analysis.
Main Results:
- HCV-infected HD patients showed a decreased CD56(dim) NK cell subset but upregulated CD69 expression.
- NK cells from both HCV-infected and uninfected HD patients exhibited poor response to LPS-induced Interferon-gamma and Tumor Necrosis Factor-alpha.
- Tumor Necrosis Factor-alpha-producing monocytes were increased in HCV-infected HD patients compared to uninfected HD patients.
Conclusions:
- Chronic HCV infection independently affects innate immunity, irrespective of hemodialysis.
- Specific alterations in NK cell subsets and monocyte cytokine production are linked to HCV infection in HD patients.
- Findings highlight the complex interplay between HCV, innate immunity, and hemodialysis.
Abstract:
Hepatitis C virus (HCV) infection is prevalent in patients with maintenance hemodialysis (HD). Although HCV affects the survival rate, antiviral treatment for HD patients is limited. Since impaired innate immunity has been proposed both in hepatitis C and in HD, we compared the immunologic features in periphery between these patients and controls. Thirty subjects were divided into four groups on the basis of HD and HCV infection. In peripheral blood mononuclear cells, NK subsets and their activation status were analyzed by flow cytometry. Cytokine productions were measured both in the culture supernatant and at the single cell level. In HCV-infected HD patients, CD56(dim) NK subset was decreased (13.1±3.7%, p=0.015) but had upregulated CD69 expression (10.4±4.2%, p=0.032) compared to the other groups. LPS effectively induced neither interferon (IFN)-γ nor tumor necrosis factor (TNF)-α in NK cells of both HCV-infected and -uninfected HD patients, while TNF-α-producing monocytes were increased in HCV-infected HD patients as compared to the uninfected. These findings indicate that chronic HCV infection affects innate immunity independently of HD.
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