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Título : Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers
Autor : Benito, José M. .
Ortiz Fernández, Mª Cruz
León, Agathe .
Sarabia Peinador, Luis Antonio
Ligos, José M. .
Montoya, María .
García, Marcial .
Ruiz Mateos, Ezequiel .
Palacios, Rosario .
Cabello, Alfonso .
Restrepo, Clara .
Rodríguez, Carmen .
Romero, Jorge del .
Leal, Manuel .
Muñoz Fernández, María A. .
Alcamí, José .
García, Felipe .
Górgolas, Miguel .
Rallón, Norma .
Publicado en: BMC Medicine. 2018
Editorial : BioMed Central
Fecha de publicación : feb-2018
ISSN : 1741-7015
DOI: 10.1186/s12916-018-1026-6
Resumen : Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. Methods A case–control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls). The partial least-squares–class modeling (PLS-CM) statistical methodology was employed to discriminate between the two groups of patients, and as a predictive model. Results Herein, we show that among T-cell homeostatic alterations, lower levels of naïve and recent thymic emigrant subsets of CD8 cells and higher levels of effector and senescent subsets of CD8 cells as well as higher levels of exhaustion of CD4 cells, measured prior to CD4 T-cell loss, predict the loss of immunological control. Conclusions These data indicate that the parameters of T-cell homeostasis may identify those EC patients with a higher proclivity to CD4 T-cell loss. Our results may open new avenues for understanding the mechanisms underlying immunological progression despite HIV replication control, and eventually, for finding a functional cure through immune-based clinical trials.
Palabras clave: Elite controllers
CD4 T-cell loss
Class modeling
T-cell homeostatic parameters
CD8 exhaustion
Licencia: https://creativecommons.org/licenses/by/4.0/
URI : http://hdl.handle.net/10259/4747
Versión del editor: https://doi.org/10.1186/s12916-018-1026-6
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