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| Home > Articles > Published articles > IL-7/IL-7R gene variants impact circulating IL-7/IL-7R homeostasis and ART-associated immune recovery status |
(Hospital Universitari Joan XXIII de Tarragona) (Institut d'Investigació Biomèdica Sant Pau) (Hospital Clínic i Provincial de Barcelona)| Date: | 2019 |
| Abstract: | A relationship between polymorphisms in genes encoding interleukin 7 (IL-7) and its cellular receptor (IL-7R) and antiretroviral therapy (ART)-associated immune recovery in HIV subjects has been previously reported. However, details of this relationship remain unclear, and the association of these polymorphisms with circulating IL-7/IL-7R levels is scarce. Here, we explored whether IL-7/IL-7R axis was associated with quantitative CD4 T-cell recovery in HIV-infected subjects. IL-7/IL-7R polymorphisms were assessed by genotyping, and multiple inheritance models were used to estimate both, their association with low pre-ART CD4 T-cell counts and incomplete immune recovery status after 48 weeks of suppressive ART. Integrated data from genetic variants association and soluble plasma IL-7/IL-7R quantification suggest that IL-7/IL-7R genotype expression could alter the homeostatic balance between soluble and membrane-bound receptors. The haplotype analyses indicates that allele combinations impacts pre-ART circulating CD4 T-cell counts, immune recovery status and the absolute increment of CD4 T-cell counts. The knowledge about how IL-7/IL-7R axis is related to quantitative CD4 T-cell recovery and immune recovery status after initiating ART could be useful regarding T-cell reservoirs investigations in HIV subjects. |
| Grants: | Instituto de Salud Carlos III RD12-0017-0005 Instituto de Salud Carlos III RD16-0025-0002 Instituto de Salud Carlos III RD16/0025/0006 Instituto de Salud Carlos III RD16-0025-0019 Instituto de Salud Carlos III RD16-0025-0020 Instituto de Salud Carlos III INT15-226 Instituto de Salud Carlos III PI10-02635 Instituto de Salud Carlos III PI13-0796 Instituto de Salud Carlos III PI14-1693 Instituto de Salud Carlos III PI16-00503 Instituto de Salud Carlos III PI16-00684 Instituto de Salud Carlos III PI19-01337 Instituto de Salud Carlos III CPII014-00025 Ministerio de Economía y Competitividad EUIN2017-89297 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR-250 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-948 Agència de Gestió d'Ajuts Universitaris i de Recerca PERIS/SLT002-16-0010101 Ministerio de Economía y Competitividad EUIN2017-89297 |
| Note: | Altres ajuts: This study would not have been possible without the collaboration of all the patients and medical and nursing staff who have taken part in the project. This work was supported by Gilead Fellowship Program GLD14/293 and GLD17/00299 and Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (Proyecto de Investigación de Excelencia; CTS2593). YMP and ERM are supported by the Servicio Andaluz de Salud through Programa Nicolás Monardes (C-0013/17 and C-0032/17, respectively). We are also grateful to GESIDA for ''Premio para Jóvenes Investigadores 2019'' to AR. Authors greatly appreciate the comments and criticisms of the anonymous reviewers that greatly helped to improve the manuscript. |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Published in: | Scientific reports, Vol. 9 Núm. 1 (january 2019) , p. 15722, ISSN 2045-2322 |
