• Eleftheria Kranidioti, Isis Ricaño-Ponce, Nikolaos Antonakos, Evdoxia Kyriazopoulou, Antigone Kotsaki, Iraklis Tsangaris, Dimitra Markopoulou, Nikoleta Rovina, Eleni Antoniadou, Ioannis Koutsodimitropoulos, George N Dalekos, Glykeria Vlachogianni, Karolina Akinosoglou, Vasilios Koulouras, Apostolos Komnos, Theano Kontopoulou, George Dimopoulos, Mihai G Netea, Vinod Kumar, and Evangelos J Giamarellos-Bourboulis.
• First Department of Internal Medicine, Evangelismos General Hospital, Athens, Greece.
• Crit. Care Med. 2024 Nov 1; 52 (11): e536e544e536-e544.

ObjectiveTo investigate the metabolomic profiles associated with different immune activation states in sepsis patients.DesignSubgroup analysis of the PROVIDE (a Personalized Randomized trial of Validation and restoration of Immune Dysfunction in severe infections and Sepsis) prospective clinical study.SettingResults of the PROVIDE study showed that patients with sepsis may be classified into three states of immune activation: 1) macrophage-activation-like syndrome (MALS) characterized by hyperinflammation, sepsis-induced immunoparalysis, and 3) unclassified or intermediate patients without severe immune dysregulation.Patients Or SubjectsTwo hundred ten patients from 14 clinical sites in Greece meeting the Sepsis-3 definitions with lung infection, acute cholangitis, or primary bacteremia.InterventionsDuring our comparison, we did not perform any intervention.Measurements And Main ResultsUntargeted metabolomics analysis was performed on plasma samples from 210 patients (a total of 1394 products). Differential abundance analysis identified 221 significantly different metabolites across the immune states. Metabolites were enriched in pathways related to ubiquinone biosynthesis, tyrosine metabolism, and tryptophan metabolism when comparing MALS to immunoparalysis and unclassified patients. When comparing MALS to unclassified, 312 significantly different metabolites were found, and pathway analysis indicated enrichment in multiple pathways. Comparing immunoparalysis to unclassified patients revealed only two differentially regulated metabolites.ConclusionsFindings suggest distinct metabolic dysregulation patterns associated with different immune dysfunctions in sepsis: the strongest metabolic dysregulation is associated with MALS.Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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