Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor, RBP4 and ZAG Are Related to CD4(+) T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy


Por: Yeregui, E, Masip, J, Vilades, C, Domingo, P, Pacheco, YM, Blanco, J, Mallolas, J, Alba, V, Vargas, M, Garcia-Pardo, G, Negredo, E, Olona, M, Vidal-Gonzalez, J, Peraire, M, Marti, A, Reverte, L, Gomez-Bertomeu, F, Leal, M, Vidal, F, Peraire, J, Rull, A

Publicada: 1 feb 2022
Resumen:
A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4(+) T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4(+) T-cell counts/mu L (controls > 200 cells/mu L and cases <= 200 cells/mu L). Immune failure recovery was considered when cases did not reach more than 250 CD4(+) T cells/mu L at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders (p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits (p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels (p < 0.01), and low circulating RBP4 concentrations were related to a low CD4(+) T-cell gain (p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4(+) T cells at 144 weeks (p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response.

Filiaciones:
Yeregui, E:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Inst Invest Sanitaria Pere Virgili IISPV, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Masip, J:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Vilades, C:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Inst Invest Sanitaria Pere Virgili IISPV, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Domingo, P:
 Hosp Santa Creu & Sant Pau, Infect Dis Unit, Barcelona 08025, Spain

Pacheco, YM:
 IBiS, Inst Biomed Seville, Lab Immunol, Seville 41013, Spain

 Univ Seville, CSIC, Virgen Rocio Univ Hosp, UGC Clin Labs, Seville 41013, Spain

Blanco, J:
 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

 AIDS Res Inst, IrsiCaixa, Badalona 08916, Spain

 Germans Trias & Pujol Res Inst IGTP, Can Ruti Campus, Badalona 08916, Spain

 Univ Cent Catalunya UVic UCC, Univ Vic, Fac Med, Infect Dis & Immun, Vic 08500, Spain

Mallolas, J:
 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

 Hosp Clin IDIBAPS, HIV Unit, Barcelona 08036, Spain

 Hosp Clin IDIBAPS, Infect Dis Serv, Barcelona 08036, Spain

Alba, V:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Vargas, M:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Garcia-Pardo, G:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Inst Invest Sanitaria Pere Virgili IISPV, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Negredo, E:
 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

 Univ Cent Catalunya UVic UCC, Univ Vic, Fac Med, Infect Dis & Immun, Vic 08500, Spain

 Hosp Badalona Germans Trias & Pujol, Fundacio Lluita Infecc, Badalona 08916, Spain

Olona, M:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Vidal-Gonzalez, J:
 Univ Barcelona UB, Barcelona 08007, Spain

Peraire, M:
 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

Marti, A:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Inst Invest Sanitaria Pere Virgili IISPV, Tarragona 43005, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Reverte, L:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Inst Invest Sanitaria Pere Virgili IISPV, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Gomez-Bertomeu, F:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Leal, M:
 Hosp Viamed Santa Angela Cruz, Internal Med Serv, Seville 41014, Spain

Vidal, F:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Inst Invest Sanitaria Pere Virgili IISPV, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Peraire, J:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Inst Invest Sanitaria Pere Virgili IISPV, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain

Rull, A:
 Hosp Univ Tarragona Joan XXIII HJ23, Infect & Immun Res Grp INIM, Tarragona 43005, Spain

 Inst Invest Sanitaria Pere Virgili IISPV, Tarragona 43005, Spain

 Univ Rovira & Virgili URV, Infect & Immun Res Grp INIM, Tarragona 43003, Spain

 Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid 28029, Spain
ISSN: 16616596





INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Editorial
MDPI, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 23 Número: 4
Páginas:
WOS Id: 000778942000001
ID de PubMed: 35216318
imagen Green Published, gold

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