Article
Plasma Metabolomics Reveals Dysregulated Metabolic Signatures in HIV-Associated Immune Reconstitution Inflammatory Syndrome
Registro en:
PEI, Luxin et al. Plasma Metabolomics Reveals Dysregulated Metabolic Signatures in HIV-Associated Immune Reconstitution Inflammatory Syndrome. Frontiers in Immunology, 2021.
1664-3224
10.3389/fimmu.2021.693074
Autor
Pei, Luxin
Fukutani, Kiyoshi Ferreira
Tibúrcio, Rafael
Rupert, Adam
Dahlstrom, Eric W.
Galindo, Frances
Laidlaw, Elizabeth
Lisco, Andrea
Manion, Maura
Andrade, Bruno de Bezerril
Resumen
Intramural Research Program of
the National Institute of Allergy and Infectious Diseases at the
National Institutes of Health (NIH). Immune 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.