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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

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@article{786bea6959df4e36a00b38f2c80e6332,
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",
abstract = "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.",
keywords = "Hepatitis C, HIV, Immune exhaustion, Soluble, Tim-3",
author = "Hedda Hoel and Thor Ueland and Malene Hove-Skovsgaard and Hartling, {Hans Jakob} and Marco Gelpi and Thomas Benfield and Henrik Ullum and Michelsen, {Annika E} and P{\aa}l Aukrust and Nielsen, {Susanne Dam} and Marius Tr{\o}seid",
note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.",
year = "2020",
month = feb,
doi = "10.1093/ofid/ofaa033",
language = "English",
volume = "7",
pages = "ofaa033",
journal = "Open Forum Infectious Diseases",
issn = "2328-8957",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection

AU - Hoel, Hedda

AU - Ueland, Thor

AU - Hove-Skovsgaard, Malene

AU - Hartling, Hans Jakob

AU - Gelpi, Marco

AU - Benfield, Thomas

AU - Ullum, Henrik

AU - Michelsen, Annika E

AU - Aukrust, Pål

AU - Nielsen, Susanne Dam

AU - Trøseid, Marius

N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - Hepatitis C

KW - HIV

KW - Immune exhaustion

KW - Soluble

KW - Tim-3

UR - http://www.scopus.com/inward/record.url?scp=85083736061&partnerID=8YFLogxK

U2 - 10.1093/ofid/ofaa033

DO - 10.1093/ofid/ofaa033

M3 - Journal article

C2 - 32055642

VL - 7

SP - ofaa033

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

SN - 2328-8957

IS - 2

M1 - ofaa033

ER -

ID: 59347785