2024-03-29T07:35:19Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/47472022-04-29T12:02:48Zcom_10259_4249com_10259_5086com_10259_2604col_10259_4250
Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers
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 .
Elite controllers
CD4 T-cell loss
Class modeling
T-cell homeostatic parameters
CD8 exhaustion
Chemistry
Mathematics
Química
Matemáticas
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.
projects RD12/0017/0031, RD16/0025/
0013, and SAF2015-66193-R as part of the Health Research and Development
Strategy, 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 European
Regional 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 a
predoctoral student co-funded by grant CP14/00198 and an Intramural
Research Scholarship from Instituto de Investigación Sanitaria-Fundación Jiménez
Díaz (IIS-FJD).
2018-03-08T11:06:50Z
2018-03-08T11:06:50Z
2018-02
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
1741-7015
http://hdl.handle.net/10259/4747
10.1186/s12916-018-1026-6
eng
BMC Medicine. 2018
https://doi.org/10.1186/s12916-018-1026-6
info:eu-repo/grantAgreement/ISCIII/RD12/0017/0031
info:eu-repo/grantAgreement/ISCIII/RD16/0025/0013
info:eu-repo/grantAgreement/SAF2015-66193-R
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
application/pdf
BioMed Central
https://riubu.ubu.es/bitstream/10259/4747/7/Benito-BMCM_2018.pdf.jpg
Hispana
TEXT
http://creativecommons.org/licenses/by/4.0/
RIUBU. Repositorio Institucional de la Universidad de Burgos
http://hdl.handle.net/10259/4747