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

Sci Rep. 2020 Sep 30;10(1):16136. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cross Infection
  • Enterotoxins / immunology
  • Female
  • Gene Expression
  • Gene Expression Profiling / methods
  • HLA-DR Antigens / metabolism
  • Humans
  • Lipopolysaccharides / pharmacology
  • Lipopolysaccharides / standards
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Proof of Concept Study
  • Sepsis / metabolism
  • Shock, Septic / classification*
  • Shock, Septic / mortality
  • Shock, Septic / pathology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Biomarkers
  • Enterotoxins
  • HLA-DR Antigens
  • Lipopolysaccharides
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • enterotoxin B, staphylococcal