Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The immune system plays a key role in sepsis onset and remains dysregulated over time in a heterogeneous manner. Here, we decipher the heterogeneity of the first week evolution of the monocyte HLA-DR (mHLA-DR) surface protein expression in septic patients, a key molecule for adaptive immunity onset. We found and verified four distinctive trajectories endotypes in a discovery (n = 276) and a verification cohort (n = 102). We highlight that 59% of septic patients exhibit low or decreasing mHLA-DR expression while in others mHLA-DR expression increased. This study depicts the first week behavior of mHLA-DR over time after sepsis onset and shows that initial and third day mHLA-DR expression measurements is sufficient for an early risk stratification of sepsis patients. These patients might benefit from immunomodulatory treatment to improve outcomes. Going further, our study introduces a way of deciphering heterogeneity of immune system after sepsis onset which is a first step to reach a more comprehensive landscape of sepsis.

Informations de copyright

Copyright © 2021 Bodinier, Peronnet, Brengel-Pesce, Conti, Rimmelé, Textoris, Vedrine, Quemeneur, Griffiths, Tan, Venet, Maucort-Boulch and Monneret.

Déclaration de conflit d'intérêts

MB, JT, KB-P, and EP are employees of bioMérieux SA, an in vitro diagnostic company. FC, TR, FV, GM, and DM-B are employees of Hospices Civils de Lyon. MB, EP, KB-P, JT, TR, FC, and GM work in a joint research unit, co funded by the Hospices Civils de Lyon and bioMérieux. LT is employee of and holds stock and shares in GlaxoSmithKline. LQ is an employee of Sanofi Pasteur. CV is employee of BIOASTER. AG is employee of ESPCI Paris. The authors declare this study received funding from bioMérieux Sanofi and GSK. The funders were involved in the REALISM study design, collection, analysis, interpretation of data, writing of report, and decision to submit the article for publication.