Articles producció científica> Medicina i Cirurgia

The persistence of low CD4/CD8 ratio chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function

  • Dades identificatives

    Identificador: imarina:9432984
    Handle: https://hdl.handle.net/20.500.11797/imarina9432984
    Autors:
    Garrido-Rodriguez, VanesaBulnes-Ramos, AngelOlivas-Martinez, IsraelPozo-Balado, Maria del MarAlvarez-Rios, Ana IsabelGutierrez, FelixIzquierdo, RebecaGarcia, FedericoTiraboschi, Juan ManuelVera-Mendez, FranciscoPeraire, JoaquimPacheco, Yolanda Maria
    Resum:
    Background: Persistence of a low CD4/CD8 ratio is associated with an increased morbimortality in people living with HIV (PLWH) under effective antiretroviral therapy. We aimed to explore the immunological significance of a persistently low CD4/CD8 ratio, even despite normal CD4 levels, and assess whether these features vary from those associated to a low nadir-CD4, another well-established predictor of disease progression. Methods: CD4-recovered PLWH were classified by CD4/CD8 ratio after three-years of ART (viral suppression, CD4>500; R < 0.8, n = 24 and R > 1.2, n = 28). sj/(3-TRECs ratio and inflammatory-related markers were quantified. PBMCs were immunophenotyped by CyTOF and functionally characterized by ELISPOT. Subjects were also reclassified depending on nadir-CD4 (N < 350/N > 350). Results: R < 0.8 showed a differential inflammatory profile compared to R > 1.2 (increased (32microglobulin, D-dimers and IP-10 before ART). R < 0.8 presented lower baseline thymic function, being inversely correlated with post-ART inflammation. R < 0.8 at follow-up showed most alterations in CD8 subsets (increasing frequency and exhibiting a senescent phenotype [e.g., CD57+, CD95+]) and enhanced T-cell IFNg/IL-2 secretion. However, comparing N < 350 to N > 350, the main features were altered functional markers in CD4 T-cells, despite no differences in maturational subsets, together with a restricted T-cell cytokine secretion pattern. Conclusion: Persistence of low CD4/CD8 ratio in successfully-treated PLWH, with normal CD4 counts, is associated with baseline inflammation and low thymic function, and it features post-therapy alterations specific to CD8 T-cells. Differently, subjects recovered from low nadir-CD4 in this setting feature post-therapy alterations on CD4 T-cells. Hence, d

  • Altres:

    Autor segons l'article: Garrido-Rodriguez, Vanesa; Bulnes-Ramos, Angel; Olivas-Martinez, Israel; Pozo-Balado, Maria del Mar; Alvarez-Rios, Ana Isabel; Gutierrez, Felix; Izquierdo, Rebeca; Garcia, Federico; Tiraboschi, Juan Manuel; Vera-Mendez, Francisco; Peraire, Joaquim; Pacheco, Yolanda Maria
    Departament: Medicina i Cirurgia
    Autor/s de la URV: Peraire Forner, José Joaquin / RULL AIXA, ANNA
    Paraules clau: T-cells Sj/β-trecs Sj/beta-trec Responses Nadir-cd4 t-cell Lung-cancer Immunological dysfunction Icam- Hiv-infection Hiv-1-infected individuals Cd4/cd8 ratio Antiretroviral therapy
    Resum: Background: Persistence of a low CD4/CD8 ratio is associated with an increased morbimortality in people living with HIV (PLWH) under effective antiretroviral therapy. We aimed to explore the immunological significance of a persistently low CD4/CD8 ratio, even despite normal CD4 levels, and assess whether these features vary from those associated to a low nadir-CD4, another well-established predictor of disease progression. Methods: CD4-recovered PLWH were classified by CD4/CD8 ratio after three-years of ART (viral suppression, CD4>500; R < 0.8, n = 24 and R > 1.2, n = 28). sj/(3-TRECs ratio and inflammatory-related markers were quantified. PBMCs were immunophenotyped by CyTOF and functionally characterized by ELISPOT. Subjects were also reclassified depending on nadir-CD4 (N < 350/N > 350). Results: R < 0.8 showed a differential inflammatory profile compared to R > 1.2 (increased (32microglobulin, D-dimers and IP-10 before ART). R < 0.8 presented lower baseline thymic function, being inversely correlated with post-ART inflammation. R < 0.8 at follow-up showed most alterations in CD8 subsets (increasing frequency and exhibiting a senescent phenotype [e.g., CD57+, CD95+]) and enhanced T-cell IFNg/IL-2 secretion. However, comparing N < 350 to N > 350, the main features were altered functional markers in CD4 T-cells, despite no differences in maturational subsets, together with a restricted T-cell cytokine secretion pattern. Conclusion: Persistence of low CD4/CD8 ratio in successfully-treated PLWH, with normal CD4 counts, is associated with baseline inflammation and low thymic function, and it features post-therapy alterations specific to CD8 T-cells. Differently, subjects recovered from low nadir-CD4 in this setting feature post-therapy alterations on CD4 T-cells. Hence, different mechanisms of disease progression could underlie these biomarkers, potentially requiring different clinical approaches. Copyright (c) 2024, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by
    Àrees temàtiques: Saúde coletiva Odontología Microbiology (medical) Microbiology Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Infectious diseases Immunology and microbiology (miscellaneous) Immunology and microbiology (all) Immunology and allergy Immunology Geografía General medicine General immunology and microbiology Farmacia Ciências biológicas iii Ciências ambientais Biotecnología
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    Adreça de correu electrònic de l'autor: joaquim.peraire@urv.cat
    Identificador de l'autor: 0000-0001-7808-5479
    Data d'alta del registre: 2025-01-28
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Referència a l'article segons font original: Journal Of Microbiology Immunology And Infection. 57 (6): 854-867
    Referència de l'ítem segons les normes APA: Garrido-Rodriguez, Vanesa; Bulnes-Ramos, Angel; Olivas-Martinez, Israel; Pozo-Balado, Maria del Mar; Alvarez-Rios, Ana Isabel; Gutierrez, Felix; Izqui (2024). The persistence of low CD4/CD8 ratio chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function. Journal Of Microbiology Immunology And Infection, 57(6), 854-867. DOI: 10.1016/j.jmii.2024.08.007
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2024
    Tipus de publicació: Journal Publications

  • Paraules clau:

    Immunology,Immunology and Allergy,Immunology and Microbiology (Miscellaneous),Infectious Diseases,Medicine (Miscellaneous),Microbiology,Microbiology (Medical)
    T-cells
    Sj/β-trecs
    Sj/beta-trec
    Responses
    Nadir-cd4 t-cell
    Lung-cancer
    Immunological dysfunction
    Icam-
    Hiv-infection
    Hiv-1-infected individuals
    Cd4/cd8 ratio
    Antiretroviral therapy
    Saúde coletiva
    Odontología
    Microbiology (medical)
    Microbiology
    Medicine (miscellaneous)
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Infectious diseases
    Immunology and microbiology (miscellaneous)
    Immunology and microbiology (all)
    Immunology and allergy
    Immunology
    Geografía
    General medicine
    General immunology and microbiology
    Farmacia
    Ciências biológicas iii
    Ciências ambientais
    Biotecnología

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