Dissertation committee:
Ηρακλής Τσαγκάρης , Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ευάγγελος Γιαμαρέλλος-Μπουρμπούλης , Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Δημόπουλος ,Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αντώνιος Παπαδόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ελένη Μπουτάτη, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Γαρυφαλλία Πουλάκου , Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Νικολέτα Ροβίνα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
The state of immune activation may guide targeted immunotherapy in sepsis. In a double-blind, double-dummy randomized clinical study, 240 patients with sepsis due to lung infection, bacteremia or acute cholangitis are subject to measurements of serum ferritin and HLA-DR/CD14. Patients with macrophage activation-like syndrome (MALS) or immunoparalysis are randomized to treatment with anakinra or recombinant interferon-gamma or placebo. 28-day mortality is the primary endpoint; sepsis immune classification is the secondary endpoint. Using ferritin >4,420 ng/ml and < 5,000 HLA-DR receptors/monocytes as biomarkers, patients are classified into MALS (20.0%), immunoparalysis (42.9%) and intermediate (37.1%). Mortality is 79.1%, 66.9% and 41.6% respectively. Survival after 7 days with SOFA score decrease is achieved in 42.9% of patients of the immunotherapy arm and 10.0% of the placebo arm (p: 0.042). Three independent immune classification strata are recognized in sepsis. MALS and immunoparalysis are proposed as stratification for personalized adjuvant immunotherapy.
Keywords:
Macrophage αctivation, Immunoparalysis, Sepsis, Ferritin
