RT Journal Article
T1 High circulating SDF-1and MCP-1 levels and genetic variations in CXCL12, CCL2 and CCR5: Prognostic signature of immune recovery status in treated HIV-positive patients.
A1 Yeregui, Elena
A1 Viladés, Consuelo
A1 Domingo, Pere
A1 Ceausu, Andra
A1 Pacheco, Yolanda María
A1 Veloso, Sergi
A1 Inciarte, Alexy
A1 Vidal-González, Judit
A1 Peraire, Maria
A1 Perpiñán, Carles
A1 Falcó, Vicenç
A1 Masip, Jenifer
A1 Alba, Verónica
A1 Vargas, Montserrat
A1 Martí, Anna
A1 Reverté, Laia
A1 Mallolas, Josep
A1 Vidal, Francesc
A1 Peraire, Joaquim
A1 Rull, Anna
K1 Chemokine receptors
K1 Chemokines
K1 HIV
K1 Polymorphisms variants
K1 Poor immune recovery
AB 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).
YR 2020
FD 2020-11-06
LK http://hdl.handle.net/10668/16573
UL http://hdl.handle.net/10668/16573
LA en
DS RISalud
RD Apr 8, 2025