Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study
Chloé Albert Vega, Guy Oriol, François Bartolo, Jonathan Lopez, Alexandre Pachot, Thomas Rimmelé, Fabienne Venet, Véronique Leray, Guillaume Monneret, Benjamin Delwarde, Karen Brengel-Pesce, Julien Textoris, François Mallet, Sophie Trouillet-Assant
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Source: Crossref
Published: Sep 30, 2020
DOI: 10.1038/s41598-020-73014-2
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Abstract 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.
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