Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/195230
Title: | Cirrhosis Hampers Early and Rapid Normalization of Natural Killer Cell Phenotype and Function in Hepatitis C Patients Undergoing Interferon-Free Therapy |
Author: | Perpiñán, Elena Pérez-Del-Pulgar, Sofía Londoño, María Carlota Mariño, Zoe Bartrés, Concepció González, Patricia García-López, Mireia Pose, Elisa Lens, Sabela Maini, Mala K Forns, Xavier Koutsoudakis, George |
Keywords: | Virus de l'hepatitis C Cirrosi hepàtica Interferó Citometria de fluxe Hepatitis C virus Hepatic cirrhosis Interferon Flow cytometry |
Issue Date: | 25-Feb-2020 |
Publisher: | Frontiers Media |
Abstract: | Background: Chronic hepatitis C virus (HCV) infection impairs natural killer (NK) cell phenotype and function. Whether restoration of NK cells occurs after successful interferon (IFN)-free therapies remains a controversial issue. Aim: To analyze how HCV-related liver cirrhosis impacts changes in NK cells prior and post-IFN-free therapies. Methods: NK cell analysis by multicolor flow cytometry was performed in HCV-infected patients with (n = 17) and without (n = 14) cirrhosis at baseline, week 4 during therapy, and weeks 12 and 48 after the end of therapy (FU12 and FU48, respectively). Non-HCV cirrhotic patients (n = 12) and healthy individuals (n = 12) served as controls. Results: At baseline, HCV cirrhotic patients presented an altered distribution of NK subsets (CD56dim and CD56bright) with higher expression of NKp46, HLA-DR, NKp30, KIR2DL2/L3, NKG2A, and CD85j receptors compared to healthy controls. All frequencies normalized by FU48, except for CD85j+ cells. Likewise, substantial alterations were detected in NK cell function assessed by (i) signal transducer and activator of transcription 1 (STAT1) and phosphorylated levels of STAT1 and STAT4, (ii) degranulation (CD107a), (iii) cytotoxicity [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)], and (iv) cytokine production [IFN-γ and tumor necrosis factor-α (TNF-α)]. Of note, NK cell function at FU48 remained partially impaired. In contrast, non-cirrhotics showed normal baseline frequencies of HLA-DR-, NKG2A-, and CD85j-expressing NK cells. Importantly, altered baseline frequencies of NK cell subsets and NKp46+ CD56dim cells, as well as NK cell function, were rapidly and completely restored. Conclusions: NK cell phenotype alterations persist after HCV eradication in cirrhotic patients, while their function is only partially restored, compromising immune restoration and immunosurveillance |
Note: | Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2020.00129 |
It is part of: | Frontiers in Immunology, 2020, vol. 11, p. 129 |
URI: | http://hdl.handle.net/2445/195230 |
Related resource: | https://doi.org/10.3389/fimmu.2020.00129 |
ISSN: | 1664-3224 |
Appears in Collections: | Articles publicats en revistes (Medicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
712017.pdf | 7.71 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License