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...

Descripción completa

Detalles Bibliográficos
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, Peraire, Joaquim, Rull, Anna, Pacheco, Yolanda María
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/219584
Acceso en línea:https://hdl.handle.net/2445/219584
Access Level:acceso abierto
Palabra clave:Infeccions per VIH
Limfòcits
HIV infections
Linfocitos
id ES_00a7ebab322bb45ae5ae3520b5ad83cf
oai_identifier_str oai:diposit.ub.edu:2445/219584
network_acronym_str ES
network_name_str España
repository_id_str
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, FranciscoPeraire, JoaquimRull, AnnaPacheco, Yolanda MaríaInfeccions per VIHLimfòcitsHIV infectionsLinfocitosBackground: 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/byElsevier BV2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/219584Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.jmii.2024.08.007Journal of Microbiology, Immunology and Infection, 2024, vol. 57, num. 6, p. 854-867https://doi.org/10.1016/j.jmii.2024.08.007cc-by-nc-nd (c) Garrido Rodríguez, Vanesa et al., 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2195842026-05-27T06:46:51Z
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
Infeccions per VIH
Limfòcits
HIV infections
Linfocitos
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
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
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
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 Infeccions per VIH
Limfòcits
HIV infections
Linfocitos
topic Infeccions per VIH
Limfòcits
HIV infections
Linfocitos
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/(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
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/219584
url https://hdl.handle.net/2445/219584
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.jmii.2024.08.007
Journal of Microbiology, Immunology and Infection, 2024, vol. 57, num. 6, p. 854-867
https://doi.org/10.1016/j.jmii.2024.08.007
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Garrido Rodríguez, Vanesa et al., 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Garrido Rodríguez, Vanesa et al., 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869402517826174976
score 15,811543

Similares en LA Referencia