RT info:eu-repo/semantics/article
T1 Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers
A1 Benito, José M. .
A1 Ortiz Fernández, Mª Cruz
A1 León, Agathe .
A1 Sarabia Peinador, Luis Antonio
A1 Ligos, José M. .
A1 Montoya, María .
A1 García, Marcial .
A1 Ruiz Mateos, Ezequiel .
A1 Palacios, Rosario .
A1 Cabello, Alfonso .
A1 Restrepo, Clara .
A1 Rodríguez, Carmen .
A1 Romero, Jorge del .
A1 Leal, Manuel .
A1 Muñoz Fernández, María A. .
A1 Alcamí, José .
A1 García, Felipe .
A1 Górgolas, Miguel .
A1 Rallón, Norma .
K1 Elite controllers
K1 CD4 T-cell loss
K1 Class modeling
K1 T-cell homeostatic parameters
K1 CD8 exhaustion
K1 Chemistry
K1 Mathematics
K1 Química
K1 Matemáticas
AB 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.ResultsHerein, 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.ConclusionsThese 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.
PB BioMed Central
SN 1741-7015
YR 2018
FD 2018-02
LK http://hdl.handle.net/10259/4747
UL http://hdl.handle.net/10259/4747
LA eng
NO projects RD12/0017/0031, RD16/0025/0013, and SAF2015-66193-R as part of the Health Research and DevelopmentStrategy, State Plan for Scientific and Technical Research and Innovation (2008–2011 and 2013–2016) and cofinanced by the Institute of Health Carlos III (ISCIII),Sub-Directorate General for Research Assessment and Promotion and EuropeanRegional Development Fund. NR is a Miguel Servet investigator from the ISCIII(CP14/00198), Madrid, Spain. C Restrepo was funded by project RD12/0017/0031 and is currently funded by project RD16/0025/0013. M García is apredoctoral student co-funded by grant CP14/00198 and an IntramuralResearch Scholarship from Instituto de Investigación Sanitaria-Fundación JiménezDíaz (IIS-FJD).
DS Repositorio Institucional de la Universidad de Burgos
RD 21-nov-2024