Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study

• Published in: Scientific reports Vol. 10; no. 1; p. 16136
• Main Authors: Albert Vega, Chloé, Oriol, Guy, Bartolo, François, Lopez, Jonathan, Pachot, Alexandre, Rimmelé, Thomas, Venet, Fabienne, Leray, Véronique, Monneret, Guillaume, Delwarde, Benjamin, Brengel-Pesce, Karen, Textoris, Julien, Mallet, François, Trouillet-Assant, Sophie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-09-2020; Nature Publishing Group
• Subjects: 631/250; 692/53; Aged; Biomarkers - blood; Cross Infection; Enterotoxins - immunology; Female; Gene Expression; Gene Expression Profiling - methods; Heterogeneity; HLA-DR Antigens - metabolism; Humanities and Social Sciences; Humans; Immune response; Life Sciences; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Lipopolysaccharides - standards; Male; Middle Aged; Monocytes - metabolism; multidisciplinary; Nosocomial infection; Nosocomial infections; Proof of Concept Study; Science; Science (multidisciplinary); Sepsis; Sepsis - metabolism; Septic shock; Shock, Septic - classification; Shock, Septic - mortality; Shock, Septic - pathology; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-73014-2

The complexity of sepsis pathophysiology hinders patient management and therapeutic decisions. In this proof-of-concept study we characterised the underlying host immune response alterations using a standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock patients, ex vivo LPS and SEB stimulations modulated, respectively, 5.3% (1/19) and 57.1% (12/21) of the pathways modulated in healthy volunteers (HV), highlighting deeper alterations induced by LPS than by SEB. SEB-based clustering, identified 3 severity-based groups of septic patients significantly different regarding mHLA-DR expression and TNFα level post-LPS, as well as 28-day mortality, and nosocomial infections. Combining the results from two independent cohorts gathering 20 HV and 60 patients, 1 cluster grouped all HV with 12% of patients. The second cluster grouped 42% of patients and contained all non-survivors. The third cluster grouped 46% of patients, including 78% of those with nosocomial infections. The molecular features of these clusters indicated a distinctive contribution of previously described genes defining a “healthy-immune response” and a “sepsis-related host response”. The third cluster was characterised by potential immune recovery that underlines the possible added value of SEB-based IFA to capture the sepsis immune response and contribute to personalised management.