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Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection

BACKGROUND: In well treated human immunodeficiency virus infection (HIV), there is a residual immune activation and immune exhaustion that may contribute to increased risk of comorbidities. T-cell immunoglobulin mucin domain-3 (Tim-3) is an inhibitory molecule involved in HIV-associated T-cell dysfu...

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Autores principales: Hoel, Hedda, Ueland, Thor, Hove-Skovsgaard, Malene, Hartling, Hans Jakob, Gelpi, Marco, Benfield, Thomas, Ullum, Henrik, Michelsen, Annika E, Aukrust, Pål, Nielsen, Susanne Dam, Trøseid, Marius
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009472/
https://www.ncbi.nlm.nih.gov/pubmed/32055642
http://dx.doi.org/10.1093/ofid/ofaa033
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author Hoel, Hedda
Ueland, Thor
Hove-Skovsgaard, Malene
Hartling, Hans Jakob
Gelpi, Marco
Benfield, Thomas
Ullum, Henrik
Michelsen, Annika E
Aukrust, Pål
Nielsen, Susanne Dam
Trøseid, Marius
author_facet Hoel, Hedda
Ueland, Thor
Hove-Skovsgaard, Malene
Hartling, Hans Jakob
Gelpi, Marco
Benfield, Thomas
Ullum, Henrik
Michelsen, Annika E
Aukrust, Pål
Nielsen, Susanne Dam
Trøseid, Marius
author_sort Hoel, Hedda
collection PubMed
description BACKGROUND: In well treated human immunodeficiency virus infection (HIV), there is a residual immune activation and immune exhaustion that may contribute to increased risk of comorbidities. T-cell immunoglobulin mucin domain-3 (Tim-3) is an inhibitory molecule involved in HIV-associated T-cell dysfunction. The Tim-3 can be cleaved to soluble Tim-3 (sTim-3) that may serve as a soluble marker of immune exhaustion. METHODS: We measured sTim-3 with enzyme-linked immunosorbent assay DuoSets in a cross-sectional cohort of 1010 people with HIV (PWH) on antiretroviral therapy (ART), and 76 controls from the Copenhagen Co-Morbidity in HIV Infection (COCOMO) study, and in a longitudinal cohort of 60 PWH before and during ART. RESULTS: In the cross-sectional cohort, levels of sTim-3 were elevated in PWH on ART compared with controls, especially in hepatitis C virus (HCV)-coinfected individuals, and were associated with HCV viremia and inflammation. In the longitudinal cohort, pretreatment sTim-3 correlated with HIV viral load and decreased after ART initiation. Pretreatment sTim-3 correlated inversely with CD4 counts, but it did not predict immunological response in multivariable analyses. CONCLUSIONS: Levels of sTim-3 decreased after ART initiation. In a cross-sectional cohort, levels of sTIM-3 were higher in PWH than in controls and were independently associated with HCV coinfection and high-sensitivity C-reactive protein, representing a potential link between immune exhaustion, inflammation, and risk of comorbidities.
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spelling pubmed-70094722020-02-13 Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection Hoel, Hedda Ueland, Thor Hove-Skovsgaard, Malene Hartling, Hans Jakob Gelpi, Marco Benfield, Thomas Ullum, Henrik Michelsen, Annika E Aukrust, Pål Nielsen, Susanne Dam Trøseid, Marius Open Forum Infect Dis Major Article BACKGROUND: In well treated human immunodeficiency virus infection (HIV), there is a residual immune activation and immune exhaustion that may contribute to increased risk of comorbidities. T-cell immunoglobulin mucin domain-3 (Tim-3) is an inhibitory molecule involved in HIV-associated T-cell dysfunction. The Tim-3 can be cleaved to soluble Tim-3 (sTim-3) that may serve as a soluble marker of immune exhaustion. METHODS: We measured sTim-3 with enzyme-linked immunosorbent assay DuoSets in a cross-sectional cohort of 1010 people with HIV (PWH) on antiretroviral therapy (ART), and 76 controls from the Copenhagen Co-Morbidity in HIV Infection (COCOMO) study, and in a longitudinal cohort of 60 PWH before and during ART. RESULTS: In the cross-sectional cohort, levels of sTim-3 were elevated in PWH on ART compared with controls, especially in hepatitis C virus (HCV)-coinfected individuals, and were associated with HCV viremia and inflammation. In the longitudinal cohort, pretreatment sTim-3 correlated with HIV viral load and decreased after ART initiation. Pretreatment sTim-3 correlated inversely with CD4 counts, but it did not predict immunological response in multivariable analyses. CONCLUSIONS: Levels of sTim-3 decreased after ART initiation. In a cross-sectional cohort, levels of sTIM-3 were higher in PWH than in controls and were independently associated with HCV coinfection and high-sensitivity C-reactive protein, representing a potential link between immune exhaustion, inflammation, and risk of comorbidities. Oxford University Press 2020-01-29 /pmc/articles/PMC7009472/ /pubmed/32055642 http://dx.doi.org/10.1093/ofid/ofaa033 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Article
Hoel, Hedda
Ueland, Thor
Hove-Skovsgaard, Malene
Hartling, Hans Jakob
Gelpi, Marco
Benfield, Thomas
Ullum, Henrik
Michelsen, Annika E
Aukrust, Pål
Nielsen, Susanne Dam
Trøseid, Marius
Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection
title Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection
title_full Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection
title_fullStr Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection
title_full_unstemmed Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection
title_short Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection
title_sort soluble t-cell immunoglobulin mucin domain-3 is associated with hepatitis c virus coinfection and low-grade inflammation during chronic human immunodeficiency virus infection
topic Major Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009472/
https://www.ncbi.nlm.nih.gov/pubmed/32055642
http://dx.doi.org/10.1093/ofid/ofaa033
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