High circulating SDF-1and MCP-1 levels and genetic variations in CXCL12, CCL2 and CCR5

The underlying mechanisms of incomplete immune reconstitution in treated HIV-positive patients are very complex and may be multifactorial, but perturbation of chemokine secretion could play a key role in CD4 T-cell turnover. We evaluated the circulating baseline and 48-week follow-up concentrations...

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Detalles Bibliográficos
Autores: Yeregui, Elena|||0000-0003-2994-4219, Viladés, Consuelo|||0000-0002-2991-9593, Domingo Pedrol, Pedro|||0000-0003-1138-5770, Ceausu, Andra, Pacheco, Yolanda M.|||0000-0002-9451-8083, Veloso Esteban, Sergio|||0000-0001-7943-1169, Inciarte, Alexy|||0000-0003-1896-3457, Vidal-González, Judit, Peraire, Maria, Perpiñán, Carles|||0000-0003-2398-3276, Falcó, Vicenç|||0000-0001-9626-0023, Masip, Jenifer|||0000-0002-9233-5195, Alba, Verónica|||0000-0002-5925-9573, Vargas Laguna, Montserrat|||0000-0001-7650-0587, Martí, Anna, Reverté Calvet, Laia|||0000-0003-4690-2387, Mallolas Masferrer, Josep|||0000-0002-8365-141X, Vidal, Francesc|||0000-0002-6692-6186, Peraire, Joaquim|||0000-0001-7808-5479, Rull, Anna|||0000-0002-8907-7754
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:284610
Acceso en línea:https://ddd.uab.cat/record/284610
https://dx.doi.org/urn:doi:10.1016/j.ebiom.2020.103077
Access Level:acceso abierto
Palabra clave:Chemokine receptors
Chemokines
HIV
Polymorphisms variants
Poor immune recovery
Descripción
Sumario:The underlying mechanisms of incomplete immune reconstitution in treated HIV-positive patients are very complex and may be multifactorial, but perturbation of chemokine secretion could play a key role in CD4 T-cell turnover. We evaluated the circulating baseline and 48-week follow-up concentrations of SDF-1/CXCL12, fractalkine/CX3CL1, MCP-1/CCL2, MIP-α/CCL3, MIP-β/CCL4 and RANTES/CCL5, and we estimated their association with CXCL12, CX3CR1, CCR2, CCL5 and CCR5 single nucleotide polymorphisms (SNPs) to investigate multiple chemokine-chemokine receptor signatures associated with immune dysregulation preceding poor immune recovery. The circulating concentrations and gene expression patterns of SDF-1/CXCL12 (CXCL12 rs1801157) and MCP-1/CCL2 (CCR2 rs1799864_814) were associated with immune recovery status. CCR2 rs1799864_814 and CCR5 rs333_814 (Δ32) determine the baseline plasma RANTES and MIP-α concentrations, respectively, in participants with poor immune response. SDF-1/CXCL12 and MCP-1/CCL2 could be considered prognostic markers of immune failure despite suppressive antiretroviral therapy. The strong linkage disequilibrium (LD) between CCR2 rs1799864_814 and CCR5 rs1800024 indicated that the alleles of each gene are inherited together more often than would be expected by chance. This work was supported by Fondo de Investigacion Sanitaria and SPANISH AIDS Research Network (ISCIII-FEDER); AGAUR and Gilead Fellowship. FV and YMP are supported by grants from the Programa de Intensificación (ISCIII) and Servicio Andaluz de Salud, respectively. JVG,EY and LR are supported by the Instituto de Salud Carlos III (ISCIII). AR is supported by Departament de Salut, Generalitat de Catalunya and by the Instituto de Salud Carlos III (ISCIII).

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