Yeregui, ElenaMasip, JeniferVilades, ConsueloDomingo, PerePacheco, Yolanda MBlanco, JuliaMallolas, JosepAlba, VeronicaVargas, MontserratGarcía-Pardo, GracianoNegredo, EugeniaOlona, MontserratVidal-Gonzalez, JuditPeraire, MariaMarti, AnnaReverte, LaiaGomez-Bertomeu, FredericLeal, ManuelVidal, FrancescPeraire, JoaquimRull, Anna2023-05-032023-05-032022-02-17Yeregui E, Masip J, Viladés C, Domingo P, Pacheco YM, Blanco J, et al. 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. Int J Mol Sci. 2022 Feb 17;23(4):2202.http://hdl.handle.net/10668/21139A 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/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4+ T cells/µL 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/HIVadipokinesantiretroviral therapyimmunodiscordant responsepoor immune recoveryAdipokinesAdultAntiretroviral Therapy, Highly ActiveApelin ReceptorsBiomarkersCD4 Lymphocyte CountCD4-Positive T-LymphocytesFemaleHIV InfectionsHIV-1HumansMaleMiddle AgedProspective StudiesRetinol-Binding Proteins, PlasmaViral Loadresearch article35216318open accessReceptores de ApelinaLinfocitos TAdipoquinasVIHCélulasSupresiónVitamina ABiomarcadoresGlicoproteínasEnsayo de inmunoadsorción enzimática10.3390/ijms230422021422-0067PMC8874604https://www.mdpi.com/1422-0067/23/4/2202/pdf?version=1645066283https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874604/pdf