Thymic Function Failure Is Associated With Human Immunodeficiency Virus Disease Progression
Por:
Ferrando-Martinez S, De Pablo-Bernal RS, De Luna-Romero M, De Ory SJ, Genebat M, Pacheco YM, Parras FJ, Montero M, Blanco JR, Gutierrez F, Santos J, Vidal F, Koup R, Muñoz-Fernández MÁ, Leal M and Ruiz-Mateos E
Publicada:
1 may 2017
Ahead of Print:
4 feb 2017
Resumen:
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.
Filiaciones:
Ferrando-Martinez S:
Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America
De Pablo-Bernal RS:
Laboratory of Immunovirology, Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville
De Luna-Romero M:
Laboratory of Immunovirology, Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville
De Ory SJ:
Molecular Immunobiology Laboratory, General Universitary Hospital Gregorio Marañon, Health Research Institute Gregorio Marañon, Spanish HIV HGM BioBank, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain
Genebat M:
Laboratory of Immunovirology, Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville
Pacheco YM:
Laboratory of Immunovirology, Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville
Parras FJ:
Infectious Disease Unit, General Universitary Hospital Gregorio Marañon, 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 (CIBIR), Logrono, Spain
:
Hospital General de Elche and Universidad Miguel Hernández, Alicante, Spain
Santos J:
Infectious Diseases Unit. Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga (IBIMA), Spain
Vidal F:
Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain
Koup R:
Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America
Muñoz-Fernández MÁ:
Molecular Immunobiology Laboratory, General Universitary Hospital Gregorio Marañon, Health Research Institute Gregorio Marañon, Spanish HIV HGM BioBank, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain
Leal M:
Laboratory of Immunovirology, Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville
Ruiz-Mateos E:
Laboratory of Immunovirology, Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville
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