High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has be...

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Main Authors: Lucero A. Ramon-Luing, Ranferi Ocaña-Guzman, Norma A. Téllez-Navarrete, Mario Preciado-García, Dámaris P. Romero-Rodríguez, Enrique Espinosa, Gustavo Reyes-Terán, Leslie Chavez-Galan
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/11/6/527
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author Lucero A. Ramon-Luing
Ranferi Ocaña-Guzman
Norma A. Téllez-Navarrete
Mario Preciado-García
Dámaris P. Romero-Rodríguez
Enrique Espinosa
Gustavo Reyes-Terán
Leslie Chavez-Galan
author_facet Lucero A. Ramon-Luing
Ranferi Ocaña-Guzman
Norma A. Téllez-Navarrete
Mario Preciado-García
Dámaris P. Romero-Rodríguez
Enrique Espinosa
Gustavo Reyes-Terán
Leslie Chavez-Galan
author_sort Lucero A. Ramon-Luing
collection DOAJ
description Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.
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spelling doaj.art-5e28937f0b1b4b9a846bd730249953822023-11-21T22:55:34ZengMDPI AGLife2075-17292021-06-0111652710.3390/life11060527High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV InfectionLucero A. Ramon-Luing0Ranferi Ocaña-Guzman1Norma A. Téllez-Navarrete2Mario Preciado-García3Dámaris P. Romero-Rodríguez4Enrique Espinosa5Gustavo Reyes-Terán6Leslie Chavez-Galan7Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoFlow Cytometry Core Facility, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoCenter for Infectious Diseases Research (CIENI), Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoImmune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.https://www.mdpi.com/2075-1729/11/6/527HIVIRISTNF-αADAMTIM-3
spellingShingle Lucero A. Ramon-Luing
Ranferi Ocaña-Guzman
Norma A. Téllez-Navarrete
Mario Preciado-García
Dámaris P. Romero-Rodríguez
Enrique Espinosa
Gustavo Reyes-Terán
Leslie Chavez-Galan
High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection
Life
HIV
IRIS
TNF-α
ADAM
TIM-3
title High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection
title_full High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection
title_fullStr High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection
title_full_unstemmed High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection
title_short High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection
title_sort high levels of tnf α and tim 3 as a biomarker of immune reconstitution inflammatory syndrome in people with hiv infection
topic HIV
IRIS
TNF-α
ADAM
TIM-3
url https://www.mdpi.com/2075-1729/11/6/527
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