High circulating SDF-1 and MCP-1 levels and genetic variations in CXCL12, CCL2 and CCR5: Prognostic signature of immune recovery status in treated HIV-positive patients
Por:
Yeregui, E, Vilades, C, Domingo, P, Ceausu, A, Pacheco, YM, Veloso, S, Inciarte, A, Vidal-Gonzalez, J, Peraire, M, Perpinan, C, Falco, V, Masip, J, Alba, V, Vargas, M, Marti, A, Reverte, L, Mallolas, J, Vidal, F, Peraire, J, Rull, A
Publicada:
1 dic 2020
Resumen:
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, fractal-kine/CX3CL1, MCP-1/CCL2, MIP-alpha/CCL3, MIP-beta/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 (032) determine the baseline plasma RANTES and MIP-alpha 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. (C) 2020 The Authors. Published by Elsevier B.V.
Filiaciones:
Yeregui, E:
Univ Rovira & Virgili, Tarragona, Spain
Inst Invest Sanitaria Pere Virgili IISPV, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Vilades, C:
Univ Rovira & Virgili, Tarragona, Spain
Inst Invest Sanitaria Pere Virgili IISPV, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Domingo, P:
Hosp Santa Creu & Sant Pau, Infect Dis Unit, Barcelona, Spain
Ceausu, A:
Univ Rovira & Virgili, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Pacheco, YM:
IBiS, Inst Biomed Seville, Lab Immunol, Seville, Spain
Univ Seville, CSIC, Virgen Rocio Univ Hosp, UGC Clin Labs, Seville, Spain
Veloso, S:
Univ Rovira & Virgili, Tarragona, Spain
Inst Invest Sanitaria Pere Virgili IISPV, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Inciarte, A:
Univ Barcelona, Hosp Clin, Dept Infect Dis, Barcelona, Spain
Vidal-Gonzalez, J:
Hosp Univ Vall dHebron HUVH, Dept Internal Med Hepatol, Barcelona, Spain
Vall dHebron Inst Recerca VHIR, Barcelona, Spain
Peraire, M:
Hosp Univ Son Espases, Palma De Mallorca, Illes Balears, Spain
Perpinan, C:
CAP St Pere, Tarragona, Spain
Falco, V:
Hosp Univ Vall DHebron, Infect Dis Dept, Barcelona, Spain
Masip, J:
Univ Rovira & Virgili, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Alba, V:
Univ Rovira & Virgili, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Vall dHebron Inst Recerca VHIR, Barcelona, Spain
Vargas, M:
Univ Rovira & Virgili, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Marti, A:
Univ Rovira & Virgili, Tarragona, Spain
Inst Invest Sanitaria Pere Virgili IISPV, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Reverte, L:
Univ Rovira & Virgili, Tarragona, Spain
Inst Invest Sanitaria Pere Virgili IISPV, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Mallolas, J:
Univ Barcelona, Hosp Clin, Dept Infect Dis, Barcelona, Spain
Vidal, F:
Univ Rovira & Virgili, Tarragona, Spain
Inst Invest Sanitaria Pere Virgili IISPV, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Peraire, J:
Univ Rovira & Virgili, Tarragona, Spain
Inst Invest Sanitaria Pere Virgili IISPV, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Rull, A:
Univ Rovira & Virgili, Tarragona, Spain
Inst Invest Sanitaria Pere Virgili IISPV, Tarragona, Spain
Hosp Univ Tarragona Joan XXIII, Tarragona, Spain
Gold, Green Published
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