PMID- 34211479 OWN - NLM STAT- MEDLINE DCOM- 20211213 LR - 20211214 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Plasma Metabolomics Reveals Dysregulated Metabolic Signatures in HIV-Associated Immune Reconstitution Inflammatory Syndrome. PG - 693074 LID - 10.3389/fimmu.2021.693074 [doi] LID - 693074 AB - 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. CI - Copyright (c) 2021 Pei, Fukutani, Tiburcio, Rupert, Dahlstrom, Galindo, Laidlaw, Lisco, Manion, Andrade and Sereti. FAU - Pei, Luxin AU - Pei L AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States. AD - Department of Biology, Johns Hopkins University, Baltimore, MD, United States. FAU - Fukutani, Kiyoshi F AU - Fukutani KF AD - Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil. AD - Laboratory of Inflammation and Biomarkers, Goncalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil. AD - Curso de Medicina, Centro Universitario Faculdade de Tecnologia e Ciencias (UniFTC), Salvador, Brazil. FAU - Tiburcio, Rafael AU - Tiburcio R AD - Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil. AD - Laboratory of Inflammation and Biomarkers, Goncalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil. AD - Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil. FAU - Rupert, Adam AU - Rupert A AD - Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States. FAU - Dahlstrom, Eric W AU - Dahlstrom EW AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT, United States. FAU - Galindo, Frances AU - Galindo F AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States. FAU - Laidlaw, Elizabeth AU - Laidlaw E AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States. FAU - Lisco, Andrea AU - Lisco A AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States. FAU - Manion, Maura AU - Manion M AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States. FAU - Andrade, Bruno B AU - Andrade BB AD - Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil. AD - Laboratory of Inflammation and Biomarkers, Goncalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil. AD - Curso de Medicina, Centro Universitario Faculdade de Tecnologia e Ciencias (UniFTC), Salvador, Brazil. AD - Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil. AD - Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. AD - Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States. FAU - Sereti, Irini AU - Sereti I AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study PT - Research Support, N.I.H., Intramural DEP - 20210615 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Biomarkers) SB - IM MH - Adult MH - Biomarkers/blood MH - *Energy Metabolism MH - Female MH - HIV/immunology MH - Host-Pathogen Interactions MH - Humans MH - Immune Reconstitution Inflammatory Syndrome/*blood/immunology/virology MH - Male MH - *Metabolome MH - *Metabolomics MH - Prospective Studies MH - Time Factors PMC - PMC8239348 OTO - NOTNLM OT - HIV OT - cell metabolism OT - immune activation OT - immune reconstitution inflammatory syndrome (IRIS) OT - metabolomics COIS- AR was employed by Leidos Biomedical Research, Inc. The authors remaining declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/07/03 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/01/01 CRDT- 2021/07/02 06:37 PHST- 2021/04/09 00:00 [received] PHST- 2021/05/27 00:00 [accepted] PHST- 2021/07/02 06:37 [entrez] PHST- 2021/07/03 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.693074 [doi] PST - epublish SO - Front Immunol. 2021 Jun 15;12:693074. doi: 10.3389/fimmu.2021.693074. eCollection 2021.