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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

AuthorsYeregui, Elena; Viladés, Consuelo; Domingo, Pere; Ceausu, Andra; Pacheco, Yolanda M. CSIC ORCID; Veloso, Sergi; Inciarte, Alexy; Vidal-González, Judit; Peraire, Maria; Perpiñán, Carles; Falcó, Vicenç; Masip, Jenifer; Alba, Verónica; Vargas, Montserrat; Marti, A.; Reverté, Laia; Mallolas, Josep; Vidal, Francesc; Peraire, Joaquim; Rull, Anna
Chemokine receptors
Poor immune recovery
Polymorphisms variants
Issue DateDec-2020
CitationEBioMedicine 62: 103077 (2020)
Abstract[Background]: 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.
[Methods]: 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.
[Findings]: 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.
[Interpretation]: 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.
Description© 2020 The Authors.
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