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Toward personalized immunotherapy in sepsis: The PROVIDE randomized clinical trial.

Cell reports. Medicine

Authors: Konstantinos Leventogiannis, Evdoxia Kyriazopoulou, Nikolaos Antonakos, Antigone Kotsaki, Iraklis Tsangaris, Dimitra Markopoulou, Inge Grondman, Nikoleta Rovina, Vassiliki Theodorou, Eleni Antoniadou, Ioannis Koutsodimitropoulos, George Dalekos, Glykeria Vlachogianni, Karolina Akinosoglou, Vassileios Koulouras, Apostolos Komnos, Theano Kontopoulou, Athanassios Prekates, Antonia Koutsoukou, Jos W M van der Meer, George Dimopoulos, Miltiades Kyprianou, Mihai G Netea, Evangelos J Giamarellos-Bourboulis

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 were subjected to measurements of serum ferritin and HLA-DR/CD14. Patients with macrophage activation-like syndrome (MALS) or immunoparalysis were randomized to treatment with anakinra or recombinant interferon-gamma or placebo. Twenty-eight-day mortality was the primary endpoint; sepsis immune classification was the secondary endpoint. Using ferritin >4,420 ng/mL and <5,000 HLA-DR receptors/monocytes as biomarkers, patients were classified into MALS (20.0%), immunoparalysis (42.9%), and intermediate (37.1%). Mortality was 79.1%, 66.9%, and 41.6%, respectively. Survival after 7 days with SOFA score decrease was 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. Clinicaltrials.gov registration NCT03332225.

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

PMID: 36384100

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