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Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status
Background: Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4(+) T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages [evaluated as liv...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262386/ https://www.ncbi.nlm.nih.gov/pubmed/30400258 http://dx.doi.org/10.3390/cells7110196 |
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author | Garcia-Broncano, Pilar Medrano, Luz Maria Berenguer, Juan González-García, Juan Jiménez-Sousa, Mª Ángeles Carrero, Ana Hontañón, Victor Guardiola, Josep M. Crespo, Manuel Quereda, Carmen Sanz, José García-Gómez, Ana Belen Jimenez, Jose Luis Resino, Salvador |
author_facet | Garcia-Broncano, Pilar Medrano, Luz Maria Berenguer, Juan González-García, Juan Jiménez-Sousa, Mª Ángeles Carrero, Ana Hontañón, Victor Guardiola, Josep M. Crespo, Manuel Quereda, Carmen Sanz, José García-Gómez, Ana Belen Jimenez, Jose Luis Resino, Salvador |
author_sort | Garcia-Broncano, Pilar |
collection | PubMed |
description | Background: Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4(+) T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages [evaluated as liver stiffness measure (LSM)] and their linear relationship. Methods: We performed a cross-sectional study on 238 HIV/HCV-coinfected patients (119 had <12.5 kPa, 73 had 12.5–25 kPa, and 46 had >25 kPa). Peripheral T-cell subsets were phenotyped by flow cytometry, plasma biomarkers were assessed by multiplex immunoassays, and LSM was assessed by transient elastography. Results: We found HIV/HCV-coinfected patients had higher values of CD4(+) Tregs (p < 0.001), memory Tregs (p ≤ 0.001), and plasma cytokine levels [IFN-γ (p ≤ 0.05) and IL-10 (p ≤ 0.01)] compared with healthy donors and HIV-monoinfected patients. In the multivariate analysis, higher LSM values were associated with reduced levels of IL-10 (adjusted arithmetic mean ratio (aAMR) = 0.83; p = 0.019), IL-2 (aAMR = 0.78; p = 0.017), TNF-α (aAMR = 0.67; p < 0.001), and IL-17A (aAMR = 0.75; p = 0.006). When we focus on HIV/HCV-coinfected patients analyzed by LSM strata, patients with ≥25 kPa had lower values of IL-2 (aAMR = 0.66; p = 0.021), TNF-α (aAMR = 0.565; p = 0.003), and IL-17A (aAMR = 0.58; p = 0.003) than patients with <12.5 kPa. Conclusion: HIV/HCV-coinfected patients showed an immunosuppressive profile compared to healthy controls and HIV-monoinfected patients. Additionally, HIV/HCV-coinfected patients with advanced cirrhosis (LSM ≥ 25 kPa) had the lowest plasma values of cytokines related to Th1 (IL-2 and TNF-α) and Th17 (IL-17A) response. |
format | Online Article Text |
id | pubmed-6262386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62623862018-12-03 Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status Garcia-Broncano, Pilar Medrano, Luz Maria Berenguer, Juan González-García, Juan Jiménez-Sousa, Mª Ángeles Carrero, Ana Hontañón, Victor Guardiola, Josep M. Crespo, Manuel Quereda, Carmen Sanz, José García-Gómez, Ana Belen Jimenez, Jose Luis Resino, Salvador Cells Article Background: Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4(+) T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages [evaluated as liver stiffness measure (LSM)] and their linear relationship. Methods: We performed a cross-sectional study on 238 HIV/HCV-coinfected patients (119 had <12.5 kPa, 73 had 12.5–25 kPa, and 46 had >25 kPa). Peripheral T-cell subsets were phenotyped by flow cytometry, plasma biomarkers were assessed by multiplex immunoassays, and LSM was assessed by transient elastography. Results: We found HIV/HCV-coinfected patients had higher values of CD4(+) Tregs (p < 0.001), memory Tregs (p ≤ 0.001), and plasma cytokine levels [IFN-γ (p ≤ 0.05) and IL-10 (p ≤ 0.01)] compared with healthy donors and HIV-monoinfected patients. In the multivariate analysis, higher LSM values were associated with reduced levels of IL-10 (adjusted arithmetic mean ratio (aAMR) = 0.83; p = 0.019), IL-2 (aAMR = 0.78; p = 0.017), TNF-α (aAMR = 0.67; p < 0.001), and IL-17A (aAMR = 0.75; p = 0.006). When we focus on HIV/HCV-coinfected patients analyzed by LSM strata, patients with ≥25 kPa had lower values of IL-2 (aAMR = 0.66; p = 0.021), TNF-α (aAMR = 0.565; p = 0.003), and IL-17A (aAMR = 0.58; p = 0.003) than patients with <12.5 kPa. Conclusion: HIV/HCV-coinfected patients showed an immunosuppressive profile compared to healthy controls and HIV-monoinfected patients. Additionally, HIV/HCV-coinfected patients with advanced cirrhosis (LSM ≥ 25 kPa) had the lowest plasma values of cytokines related to Th1 (IL-2 and TNF-α) and Th17 (IL-17A) response. MDPI 2018-11-02 /pmc/articles/PMC6262386/ /pubmed/30400258 http://dx.doi.org/10.3390/cells7110196 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Garcia-Broncano, Pilar Medrano, Luz Maria Berenguer, Juan González-García, Juan Jiménez-Sousa, Mª Ángeles Carrero, Ana Hontañón, Victor Guardiola, Josep M. Crespo, Manuel Quereda, Carmen Sanz, José García-Gómez, Ana Belen Jimenez, Jose Luis Resino, Salvador Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status |
title | Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status |
title_full | Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status |
title_fullStr | Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status |
title_full_unstemmed | Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status |
title_short | Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status |
title_sort | dysregulation of the immune system in hiv/hcv-coinfected patients according to liver stiffness status |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262386/ https://www.ncbi.nlm.nih.gov/pubmed/30400258 http://dx.doi.org/10.3390/cells7110196 |
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