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

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 wh...

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Autores: Garrido Rodríguez, Vanesa, Bulnes Ramos, Ángel, Olivas Martínez, Israel, Pozo Balado, María del Mar, Álvarez Ríos, Ana Isabel, Gutiérrez, Félix, Izquierdo, Rebeca, García, federico, Tiraboschi, Juan Manuel, Vera Méndez, Francisco Jesús, Peraire, Joaquim, Rull, Anna, Pacheco, Yolanda María
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Universidad Católica San Antonio de Murcia (UCAM)
Repositorio:RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia
OAI Identifier:oai:repositorio.ucam.edu:10952/9063
Acesso em linha:http://hdl.handle.net/10952/9063
Access Level:acceso abierto
Palavra-chave:CD4/CD8 ratio
HIV-Infection
Immunological dysfunction
Nadir-CD4 T-cell
sj/β-TRECs
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spelling The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic functionGarrido Rodríguez, VanesaBulnes Ramos, ÁngelOlivas Martínez, IsraelPozo Balado, María del MarÁlvarez Ríos, Ana IsabelGutiérrez, FélixIzquierdo, RebecaGarcía, federicoTiraboschi, Juan ManuelVera Méndez, Francisco JesúsPeraire, JoaquimRull, AnnaPacheco, Yolanda MaríaCD4/CD8 ratioHIV-InfectionImmunological dysfunctionNadir-CD4 T-cellsj/β-TRECsBackground: 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/β-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 β2-microglobulin, 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 IFNγ/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.MedicinaMedicina2024info:eu-repo/semantics/articlehttp://hdl.handle.net/10952/9063reponame:RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murciainstname:Universidad Católica San Antonio de Murcia (UCAM)Inglésinfo:eu-repo/semantics/openAccessoai:repositorio.ucam.edu:10952/90632026-06-07T18:35:21Z
dc.title.none.fl_str_mv The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function
title The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function
spellingShingle The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function
Garrido Rodríguez, Vanesa
CD4/CD8 ratio
HIV-Infection
Immunological dysfunction
Nadir-CD4 T-cell
sj/β-TRECs
title_short The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function
title_full The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function
title_fullStr The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function
title_full_unstemmed The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function
title_sort The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function
dc.creator.none.fl_str_mv Garrido Rodríguez, Vanesa
Bulnes Ramos, Ángel
Olivas Martínez, Israel
Pozo Balado, María del Mar
Álvarez Ríos, Ana Isabel
Gutiérrez, Félix
Izquierdo, Rebeca
García, federico
Tiraboschi, Juan Manuel
Vera Méndez, Francisco Jesús
Peraire, Joaquim
Rull, Anna
Pacheco, Yolanda María
author Garrido Rodríguez, Vanesa
author_facet Garrido Rodríguez, Vanesa
Bulnes Ramos, Ángel
Olivas Martínez, Israel
Pozo Balado, María del Mar
Álvarez Ríos, Ana Isabel
Gutiérrez, Félix
Izquierdo, Rebeca
García, federico
Tiraboschi, Juan Manuel
Vera Méndez, Francisco Jesús
Peraire, Joaquim
Rull, Anna
Pacheco, Yolanda María
author_role author
author2 Bulnes Ramos, Ángel
Olivas Martínez, Israel
Pozo Balado, María del Mar
Álvarez Ríos, Ana Isabel
Gutiérrez, Félix
Izquierdo, Rebeca
García, federico
Tiraboschi, Juan Manuel
Vera Méndez, Francisco Jesús
Peraire, Joaquim
Rull, Anna
Pacheco, Yolanda María
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CD4/CD8 ratio
HIV-Infection
Immunological dysfunction
Nadir-CD4 T-cell
sj/β-TRECs
topic CD4/CD8 ratio
HIV-Infection
Immunological dysfunction
Nadir-CD4 T-cell
sj/β-TRECs
description 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/β-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 β2-microglobulin, 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 IFNγ/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.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10952/9063
url http://hdl.handle.net/10952/9063
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia
instname:Universidad Católica San Antonio de Murcia (UCAM)
instname_str Universidad Católica San Antonio de Murcia (UCAM)
reponame_str RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia
collection RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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