Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers

Autor: Benito, José M., Ortiz, María C., León García, Agathe, Sarabia, Luis A., Ligos, José M., Montoya, María, García, Marcial, Ruiz Mateos, Ezequiel, Palacios, Rosario, Cabello, Alfonso, Restrepo, Clara, Rodríguez, Carmen, del Romero, Jorge, Leal, Manuel, Munoz Fernández, María A., Alcamí, José, García Alcaide, Felipe, Górgolas, Miguel, Rallón, Norma, ECRIS integrated in the Spanish AIDS Research Netw
Přispěvatelé: Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Ministerio de Economía y Competitividad (España), European Regional Development Fund (ERDF/FEDER), Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz
Rok vydání: 2018
Předmět:
Zdroj: Dipòsit Digital de la UB
Universidad de Barcelona
Repisalud
Instituto de Salud Carlos III (ISCIII)
BMC Medicine
BMC Medicine, Vol 16, Iss 1, Pp 1-12 (2018)
Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid
Repositorio Institucional de la Universidad de Burgos (RIUBU)
instname
Popis: 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).
Databáze: OpenAIRE
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