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dc.contributor.authorBenito, José M. .
dc.contributor.authorOrtiz Fernández, Mª Cruz 
dc.contributor.authorLeón, Agathe .
dc.contributor.authorSarabia Peinador, Luis Antonio 
dc.contributor.authorLigos, José M. .
dc.contributor.authorMontoya, María .
dc.contributor.authorGarcía, Marcial .
dc.contributor.authorRuiz Mateos, Ezequiel .
dc.contributor.authorPalacios, Rosario .
dc.contributor.authorCabello, Alfonso .
dc.contributor.authorRestrepo, Clara .
dc.contributor.authorRodríguez, Carmen .
dc.contributor.authorRomero, Jorge del .
dc.contributor.authorLeal, Manuel .
dc.contributor.authorMuñoz Fernández, María A. .
dc.contributor.authorAlcamí, José .
dc.contributor.authorGarcía, Felipe .
dc.contributor.authorGórgolas, Miguel .
dc.contributor.authorRallón, Norma .
dc.date.accessioned2018-03-08T11:06:50Z
dc.date.available2018-03-08T11:06:50Z
dc.date.issued2018-02
dc.identifier.issn1741-7015
dc.identifier.urihttp://hdl.handle.net/10259/4747
dc.description.abstractDespite 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.en
dc.description.sponsorshipprojects 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).en
dc.format.mimetypeapplication/pdf
dc.language.isoenges
dc.publisherBioMed Centralen
dc.relation.ispartofBMC Medicine. 2018en
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectElite controllersen
dc.subjectCD4 T-cell lossen
dc.subjectClass modelingen
dc.subjectT-cell homeostatic parametersen
dc.subjectCD8 exhaustionen
dc.subject.otherChemistryen
dc.subject.otherMathematicsen
dc.subject.otherQuímicaes
dc.subject.otherMatemáticases
dc.titleClass-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllersen
dc.typeinfo:eu-repo/semantics/article
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.relation.publisherversionhttps://doi.org/10.1186/s12916-018-1026-6
dc.identifier.doi10.1186/s12916-018-1026-6
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/RD12/0017/0031
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/RD16/0025/0013
dc.relation.projectIDinfo:eu-repo/grantAgreement/SAF2015-66193-R
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersionen


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