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
Elena Yeregui,
Consuelo Viladés,
Pere Domingo,
Andra Ceausu,
Yolanda María Pacheco,
Sergi Veloso,
Alexy Inciarte,
Judit Vidal-González,
Maria Peraire,
Carles Perpiñán,
Vicenç Falcó,
Jenifer Masip,
Verónica Alba,
Montserrat Vargas,
Anna Martí,
Laia Reverté,
Josep Mallolas,
Francesc Vidal,
Joaquim Peraire,
Anna Rull
Affiliations
Elena Yeregui
Universitat Rovira i Virgili, Tarragona, Spain; Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
Consuelo Viladés
Universitat Rovira i Virgili, Tarragona, Spain; Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
Pere Domingo
Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Andra Ceausu
Universitat Rovira i Virgili, Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
Yolanda María Pacheco
Laboratory of Immunology, Institute of Biomedicine of Seville, IBiS, Seville, Spain; UGC Clinical Laboratories, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
Sergi Veloso
Universitat Rovira i Virgili, Tarragona, Spain; Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
Alexy Inciarte
Department of Infectious Diseases, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain
Judit Vidal-González
Department of Internal Medicine - Hepatology, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain; Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
Maria Peraire
Hospital Universitari Son Espases, Palma, Illes balears, Spain
Universitat Rovira i Virgili, Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
Verónica Alba
Universitat Rovira i Virgili, Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
Montserrat Vargas
Universitat Rovira i Virgili, Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
Anna Martí
Universitat Rovira i Virgili, Tarragona, Spain; Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
Laia Reverté
Universitat Rovira i Virgili, Tarragona, Spain; Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
Josep Mallolas
Department of Infectious Diseases, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain
Francesc Vidal
Universitat Rovira i Virgili, Tarragona, Spain; Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain; Corresponding author: Francesc Vidal Marsal, Department of Internal Medicine and Infectious Diseases, Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, c/Mallafré Guasch, 4; Tarragona, Spain 43007
Joaquim Peraire
Universitat Rovira i Virgili, Tarragona, Spain; Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
Anna Rull
Universitat Rovira i Virgili, Tarragona, Spain; Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain; Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
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. Funding: 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).
