Dissertation committee:
Ευάγγελος Γιαμαρέλλος-Μπουρμπούλης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Δημοπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ηρακλής Τσαγκάρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ελένη Μπουτάτη, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ελένη Μάγειρα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Βάϊα Λαμπαδιάρη, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Αντώνιος Παπαδόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Objectives: To investigate the metabolomic profiles associated with different immune activation states in sepsis patients.
Design: Prospective clinical study
Setting: Results of the PROVIDE study showed that patients with sepsis may be classified into three states of immune activation: (i) macrophage activation-like syndrome (MALS) characterized by hyperinflammation, (ii) sepsis-induced immunoparalysis, and (iii) unclassified or intermediate patients without severe immune dysregulation.
Subjects: 210 patients from 14 clinical sites in Greece meeting the Sepsis-3 definitions with lung infection, acute cholangitis or primary bacteremia.
Measurements: Untargeted 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.
Results: 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 patients, 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.
Conclusions: Findings suggest distinct metabolic dysregulation patterns associated with different immune dysfunctions in sepsis: the strongest metabolic dysregulation is associated with MALS.
Keywords:
Sepsis , Macrophage activation-like syndrome , Immunoparalysis , Metabolomics , Metabolites
