df56962b9a39698f65e0fd339302f811 290611.pdf e58839a6173020c88ae825a7dda8dd9d3e445770 290611.pdf 8573bfa6da9f88a5f9fe699bc1076f70ce98b1c38986c670c0ceb91f55f87389 290611.pdf Title: 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 Subject: 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/L (controls > 200 cells/L and cases 200 cells/L). Immune failure recovery was considered when cases did not reach more than 250 CD4+ T cells/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. Keywords: adipokines; antiretroviral therapy; HIV; immunodiscordant response; poor immune recovery Author: Elena Yeregui, Jenifer Masip, Consuelo Viladés, Pere Domingo, Yolanda M. Pacheco, Julià Blanco, Josep Mallolas, Verónica Alba, Montserrat Vargas, Graciano García-Pardo, Eugènia Negredo, Montserrat Olona, Judit Vidal-González, Maria Peraire, Anna Martí, Laia Reverté, Fréderic Gómez-Bertomeu, Manuel Leal, Francesc Vidal, Joaquim Peraire and Anna Rull Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Feb 17 03:40:16 2022 CET ModDate: Thu Feb 17 03:51:23 2022 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 6172214 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ETLENW+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 CYVJLM+VnURWPalladioL Type 1 Custom yes yes no 15 0 CNNXMJ+EURM10 Type 1 Builtin yes yes no 19 0 RHTUZI+URWPalladioL-Bold Type 1 Custom yes yes no 23 0 HNBQJR+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 KOHXXY+URWPalladioL-Ital Type 1 Custom yes yes no 32 0 ZHLHTP+CMSY10 Type 1 Builtin yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 44 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 48 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 52 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 64 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 67 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 92 0 NEMKEE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 184 0 NEMKFG+PalatinoLinotype TrueType WinAnsi yes yes no 187 0 NEMKGI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 190 0 NEMKEE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 290 0 NEMKFG+PalatinoLinotype TrueType WinAnsi yes yes no 293 0 NEMKGI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 296 0 CIDFont+F3 CID TrueType Identity-H yes no yes 368 0 CIDFont+F1 CID TrueType Identity-H yes no yes 376 0 CIDFont+F2 CID TrueType Identity-H yes no yes 384 0 CIDFont+F3 CID TrueType Identity-H yes no yes 400 0 CIDFont+F1 CID TrueType Identity-H yes no yes 408 0 CIDFont+F2 CID TrueType Identity-H yes no yes 416 0 NEMKEE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 477 0 NEMKFG+PalatinoLinotype TrueType WinAnsi yes yes no 480 0 NEMKGI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 483 0 HCKCGK+PalatinoLinotype TrueType WinAnsi yes yes no 544 0 HCKDGG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 547 0 QKYDFU+MSAM10 Type 1 Builtin yes yes no 557 0 HCKCGK+PalatinoLinotype TrueType WinAnsi yes yes no 568 0 HCKDGG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 571 0 HCKCGK+PalatinoLinotype TrueType WinAnsi yes yes no 585 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-04-13 02:43:50 CEST RepresentationInformation: 290611.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-04-11 17:01:05 CEST Size: 6172214 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 804 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Patient Characteristics Destination: subsection.2.1 Item: Title: Low APLNR and ZAG Concentrations Predicted Discordant Responses to ART Destination: subsection.2.2 Item: Title: APLNR and ZAG Concentrations Were Related to Poor Immune Progression Destination: subsection.2.3 Item: Title: APLNR and RBP4 Were Validated as Predictive Biomarkers of a Discordant Response Destination: subsection.2.4 Item: Title: ART Affected FABP4, Omentin, and Resistin Concentrations Destination: subsection.2.5 Item: Title: The Potential Effects of Different Antiretroviral Drugs on Adipokine Concentrations Destination: subsection.2.6 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Study Design and Participants Destination: subsection.4.1 Item: Title: General Laboratory Measurements Destination: subsection.4.2 Item: Title: Adipokine Measurements Destination: subsection.4.3 Item: Title: Statistical Analyses Destination: subsection.4.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: 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 Author: Elena Yeregui, Jenifer Masip, Consuelo Viladés, Pere Domingo, Yolanda M. Pacheco, Julià Blanco, Josep Mallolas, Verónica Alba, Montserrat Vargas, Graciano García-Pardo, Eugènia Negredo, Montserrat Olona, Judit Vidal-González, Maria Peraire, Anna Martí, Laia Reverté, Fréderic Gómez-Bertomeu, Manuel Leal, Francesc Vidal, Joaquim Peraire and Anna Rull Subject: 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/L (controls > 200 cells/L and cases 200 cells/L). Immune failure recovery was considered when cases did not reach more than 250 CD4+ T cells/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. 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