Thymic Function Failure Is Associated With Human Immunodeficiency Virus Disease Progression

Fecha de publicación: 01/05/2017

Autores de IIS La Fe

Marta Montero Alonso

Autor

Participantes ajenos a IIS La Fe

Ferrando-Martinez S
De Pablo-Bernal RS
De Luna-Romero M
De Ory SJ
Genebat M
Pacheco YM
Parras FJ
Blanco JR
Gutierrez F
Santos J
Vidal F
Koup RA
Munoz-Fernandez MA
Leal M
Ruiz-Mateos E

Grupos

Investigacion clínica en enfermedades crónicas e Infección por el VIH

Investigador establecido

Marta Montero Alonso

Abstract

Background. Thymic function has been mainly analyzed with surrogate peripheral markers affected by peripheral T-cell expansion, making it difficult to assess the role of thymic failure in human immunodeficiency virus (HIV) disease progression. The assay of signal-joint/D beta J beta T-cell rearrangement excision circles (sj/beta-TREC ratio) overcomes this limitation but has only been assayed in small cohorts. Thus, the aim of this study was to determine the role of thymic function, measured by the sj/beta-TREC ratio, on CD4 T-cell maintenance in prospective HIV cohorts that include patients with a wide age range and different immunological phenotypes. Methods. Seven hundred seventy-four patients including typical progressors, long-term nonprogressors (LTNPs), and vertically HIV-infected subjects were analyzed. Thymic function was quantified in peripheral blood samples using the sj/beta-TREC ratio. Associations between thymic function and CD4 T-cell dynamics and combination antiretroviral therapy (cART) onset were analyzed using linear, logistic, and Cox proportional hazard models. Results. Thymic function failure (sj/beta-TREC ratio <10) was independently associated with HIV progression. In agreement, patients with distinctive high CD4 T-cell levels and low progression rates (vertically HIV-infected patients and LTNPs, including HIV controllers) had significantly higher thymic function levels whereas patients with thymic function failure had lower CD4 T-cell levels, lower nadir, and faster CD4 T-cell decay. Conclusions. This work establishes the relevance of thymic function, measured by sj/beta-TREC ratio, in HIV disease progression by analyzing a large number of patients in 3 cohorts with different HIV disease progression phenotypes. These results support and help to understand the mechanisms underlying the rationale of early cART onset.

Datos de la publicación

ISSN/ISSNe:: 1058-4838, 1537-6591
Tipo:: Article
Páginas:: 1191-1197
DOI:: 10.1093/cid/cix095
Factor de Impacto:: 5,051 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Ferrando-Martinez S:: Immunology Laboratory, Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
De Pablo-Bernal RS:: Laboratory of Immunovirology, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital/CSIC/University of Seville, Spain
De Luna-Romero M:: Laboratory of Immunovirology, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital/CSIC/University of Seville, Spain
De Ory SJ:: Molecular Immunobiology Laboratory, General University Hospital Gregorio Maranon, Health Research Institute Gregorio Maranon, Spanish HIV HGM BioBank, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, Madrid, Spain
Genebat M:: Laboratory of Immunovirology, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital/CSIC/University of Seville, Spain
Pacheco YM:: Laboratory of Immunovirology, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital/CSIC/University of Seville, Spain
Parras FJ:: Infectious Disease Unit, General Universitary Hospital Gregorio Maranon, Madrid, Spain
Montero M:: Infectious Disease Unit, Polytechnic and University Hospital La Fe, Valencia, Spain
Blanco JR:: Infectious Diseases Department, Hospital San Pedro, Center for Biomedical Research of La Rioja, Logrono, Spain
Gutierrez F:: Hospital General de Elche and Universidad Miguel Hernandez, Alicante, Spain
Santos J:: Infectious Diseases Unit, Virgen de la Victoria University Hospital, Instituto de Investigacion Biomedica de Malaga, Spain
Vidal F:: Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Spain
Koup RA:: Immunology Laboratory, Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Munoz-Fernandez MA:: Molecular Immunobiology Laboratory, General University Hospital Gregorio Maranon, Health Research Institute Gregorio Maranon, Spanish HIV HGM BioBank, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, Madrid, Spain
Leal M:: Laboratory of Immunovirology, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital/CSIC/University of Seville, Spain
Ruiz-Mateos E:: Laboratory of Immunovirology, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital/CSIC/University of Seville, Spain