Naïve/Effector CD4 T cell ratio as a useful predictive marker of immune reconstitution in late presenter HIV patients: A multicenter study

Autoři: Veronica Bordoni aff001;  Bruno Brando aff002;  Pierluca Piselli aff001;  Olindo Forini aff001;  Federico Enrico Perna aff003;  Umberto Atripaldi aff004;  Sara Carputo aff004;  Federica Garziano aff004;  Elisabetta Trento aff005;  Giovanna D’Agosto aff005;  Alessandra Latini aff005;  Manuela Colafigli aff005;  Antonio Cristaudo aff005;  Alessandra Sacchi aff001;  Massimo Andreoni aff006;  Gabriella De Carli aff007;  Nicoletta Orchi aff007;  Sandro Grelli aff008;  Arianna Gatti aff002;  Carlotta Cerva aff009;  Antonella Minutolo aff009;  Marina Potestà aff009;  Maria Luisa Di Martino aff010;  Francesco Ortu aff011;  Paola Selva aff012;  Laura Del Pup aff013;  Irene Guarnori aff014;  Patrizia Lorenzini aff007;  Giusy Capuano aff015;  Andrea Antinori aff007;  Chiara Agrati aff001
Působiště autorů: INMI L. Spallanzani IRCCS, Rome, Italy aff001;  Blood Transfusion Center, Legnano General Hospital, Legnano, Italy aff002;  Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy aff003;  Department of Clinical Biochemistry, Ospedali dei Colli, Naples, Italy aff004;  San Gallicano Dermatological Institute IRCCS, Rome, Italy aff005;  Clinical Infectious Diseases, Department of System Medicine, University of Rome “Tor Vergata”, Rome, Italy aff006;  Clinical Department, INMI L Spallanzani IRCCS, Rome, Italy aff007;  Clinical Microbiology and Virology Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy aff008;  General Pathology and Immunology, Department of Biology, University of Rome “Tor Vergata”, Rome, Italy aff009;  Laboratorio di Allergologia e Diagnostica dell'HIV della S.C. Medicina Interna, Azienda Ospedaliero Universitaria Cagliari, Cagliari, Italy aff010;  Dipartimento di Medicina, Azienda Ospedaliero Universitaria Cagliari, Cagliari, Cagliari, Italy aff011;  Laboratorio Unico Metropolitano (LUM), Azienda USL, Bologna, Italy aff012;  UOC Anatomia Patologica, Azienda ULSS2 Marca Trevigiana, Treviso, Italy aff013;  Department of Transfusion Medicine and Hematology, Azienda Ospedaliera della Provincia di Lecco, Alessandro Manzoni Hospital, Lecco, Italy aff014;  Becton Dickinson Italia, Milan, Italy aff015
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225415


A significant proportion of HIV-infected patients experiencing a late diagnosis highlights the need to define immunological protocols able to help the clinicians in identifying patients at higher risk for immunological failure. The aim of the study was to evaluate the feasibility of easy cytometric tests in defining the effect of antiretroviral treatment (cART) on immunological homeostasis and in identifying predictive markers of early immune recovery. Chronic HIV infected patients (n = 202) were enrolled in a prospective multicentric study, and their immunological profile was studied before (w0) and after 24 weeks (w24) of antiretroviral treatment (cART) using a standardized flow cytometric panel. Based on CD4 T cell count before treatment, patients were divided in late (LP: CD4 <350/mmc), intermediate (IP: 350/mmc<CD4<500/mmc) and early (EP: CD4 >500/mmc) presenters. In all groups, cART introduction increased CD4 and CD4/CD8 T cell ratio, naïve T cell (CD4 and CD8) and CD127-expressing CD4 T cells. In parallel, cART significantly reduced effector memory T cells (CD4 and CD8) and T cell activation (CD38+CD8 and CD95+CD4 T cells). Moreover, the frequency of Naïve and Effector CD4 T cells before treatment correlated with several immune parameters key associated with the pathogenesis of HIV, thus mirroring the health of immune system. Interestingly, we identified the Naïve/Effector CD4 T cell ratio (N/EM) at w0 as a marker able to predict early immune recovery. Specifically, in LP, N/EM ratio was significantly higher in immunological responder patients (CD4>500/mmc at w24) when compared to immunological non responder (CD4 T cells <500/mmc at w24). Finally, a multivariate analysis indicates that after 24w patients with N/EM ratio higher than 1.86 at w0 recovered 96 CD4 T cells more than those with N/EM ratio lower than 0.46. Altogether, our data define an easy protocol able to define reliable immunological markers useful for the characterization of immune profile in viremic HIV patients and identify the naïve/effector CD4 T cell ratio as a new tool able to predict an early immune reconstitution potential.

Klíčová slova:

Cell enumeration techniques – Cytotoxic T cells – HIV diagnosis and management – HIV infections – Immune response – T cells – T helper cells


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