Thymic Function Failure Is Associated With Human Immunodeficiency Virus Disease Progression
Open Access
- 4 February 2017
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 64 (9), 1191-1197
- https://doi.org/10.1093/cid/cix095
Abstract
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/DβJβ T-cell rearrangement excision circles (sj/β-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/β-TREC ratio, on CD4 T-cell maintenance in prospective HIV cohorts that include patients with a wide age range and different immunological phenotypes. 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/β-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. Thymic function failure (sj/β-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. This work establishes the relevance of thymic function, measured by sj/β-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.Keywords
This publication has 33 references indexed in Scilit:
- A new tool for the paediatric HIV research: general data from the Cohort of the Spanish Paediatric HIV Network (CoRISpe)BMC Infectious Diseases, 2013
- Premature immunosenescence in HIV-infected patients on highly active antiretroviral therapy with low-level CD4 T cell repopulationJournal of Antimicrobial Chemotherapy, 2009
- The Spanish HIV BioBank: a model of cooperative HIV researchRetrovirology, 2009
- Thymopoiesis in elderly human is associated with systemic inflammatory statusAGE, 2009
- Human CD4+ T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune functionThe Journal of Experimental Medicine, 2009
- Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infectionBlood, 2006
- HIV Infection Rapidly Induces and Maintains a Substantial Suppression of Thymocyte ProliferationImmunity, 2004
- Persistent immune activation in HIV-1 infection is associated with progression to AIDSAIDS, 2003
- T-cell repopulation and thymic volume in HIV-1–infected adult patients after highly active antiretroviral therapyBlood, 2002
- Hypertrophy of the thymus and restoration of immune functions in mice and rats by gonadectomyMechanisms of Ageing and Development, 1989