Plasma Metabolomics Reveals Dysregulated Metabolic Signatures in HIV-Associated Immune Reconstitution Inflammatory Syndrome

dc.creatorPei, Luxin
dc.creatorFukutani, Kiyoshi Ferreira
dc.creatorTibúrcio, Rafael
dc.creatorRupert, Adam
dc.creatorDahlstrom, Eric W.
dc.creatorGalindo, Frances
dc.creatorLaidlaw, Elizabeth
dc.creatorLisco, Andrea
dc.creatorManion, Maura
dc.creatorAndrade, Bruno de Bezerril
dc.date2021-07-08T17:12:09Z
dc.date2021-07-08T17:12:09Z
dc.date2021
dc.date.accessioned2023-09-26T21:15:36Z
dc.date.available2023-09-26T21:15:36Z
dc.identifierPEI, Luxin et al. Plasma Metabolomics Reveals Dysregulated Metabolic Signatures in HIV-Associated Immune Reconstitution Inflammatory Syndrome. Frontiers in Immunology, 2021.
dc.identifier1664-3224
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/48073
dc.identifier10.3389/fimmu.2021.693074
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8871656
dc.descriptionIntramural Research Program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH).
dc.descriptionImmune reconstitution inflammatory syndrome (IRIS) is an inflammatory complication associated with an underlying opportunistic infection that can be observed in HIV-infected individuals shortly after the initiation of antiretroviral therapy, despite successful suppression of HIV viral load and CD4+ T cell recovery. Better understanding of IRIS pathogenesis would allow for targeted prevention and therapeutic approaches. In this study, we sought to evaluate the metabolic perturbations in IRIS across longitudinal time points using an unbiased plasma metabolomics approach as well as integrated analyses to include plasma inflammatory biomarker profile and whole blood transcriptome. We found that many lipid and amino acid metabolites differentiated IRIS from non-IRIS conditions prior to antiretroviral therapy and during the IRIS event, implicating the association between oxidative stress, tryptophan pathway, and lipid mediated signaling and the development of IRIS. Lipid and amino acid metabolic pathways also significantly correlated with inflammatory biomarkers such as IL-12p70 and IL-8 at the IRIS event, indicating the role of cellular metabolism on cell type specific immune activation during the IRIS episode and in turn the impact of immune activation on cellular metabolism. In conclusion, we defined the metabolic profile of IRIS and revealed that perturbations in metabolism may predispose HIV-infected individuals to IRIS development and contribute to the inflammatory manifestations during the IRIS event. Furthermore, our findings expanded our current understanding IRIS pathogenesis and highlighted the significance of lipid and amino acid metabolism in inflammatory complications.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFrontiers Media
dc.rightsopen access
dc.subjectSíndrome inflamatória de reconstituição imune
dc.subjectMetabolismo
dc.subjectMetabolômica
dc.subjectPlasma
dc.subjectHIV
dc.subjectImmune reconstitution inflammatory syndrome
dc.subjectCell metabolism
dc.subjectMetabolomics
dc.subjectImmune activation
dc.subjectHIV
dc.titlePlasma Metabolomics Reveals Dysregulated Metabolic Signatures in HIV-Associated Immune Reconstitution Inflammatory Syndrome
dc.typeArticle


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