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...
| Autores: | , , , , , , , , , , , , |
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| 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 |
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oai:diposit.ub.edu:2445/219584 |
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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 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 Infeccions per VIH Limfòcits HIV infections Linfocitos 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 Elsevier BV https://hdl.handle.net/2445/219584 |
| 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 |
| 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 |
| topic |
Infeccions per VIH Limfòcits HIV infections Linfocitos |
| topic_facet |
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 |
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2024 |
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article |
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publishedVersion |
| url |
https://hdl.handle.net/2445/219584 |
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openAccess |
| publisher |
Elsevier BV |
| institution |
Universidad de Barcelona |
| collection |
Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
| instname_str |
Universidad de Barcelona |
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1878430679300046848 |
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2024 |
| author_browse |
Bulnes Ramos, Ángel García, Federico Garrido Rodríguez, Vanesa Gutiérrez, Félix Izquierdo, Rebeca Olivas Martínez, Israel Pacheco, Yolanda María Peraire, Joaquim Pozo Balado, María Del Mar Rull, Anna Tiraboschi, Juan Manuel Vera Méndez, Francisco Álvarez Ríos, Ana Isabel |
| publisherStr |
Elsevier BV |
| score |
6,924472 |