Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study
| Autor: | Fabienne Venet, François Mallet, Jonathan Lopez, Sophie Trouillet-Assant, Guillaume Monneret, Véronique Leray, Alexandre Pachot, François Bartolo, Karen Brengel-Pesce, Chloé Albert Vega, Julien Textoris, Thomas Rimmelé, Benjamin Delwarde, Guy Oriol |
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| Přispěvatelé: | Bio-Mérieux [Marcy l'Etoile], BIOMERIEUX, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Edouard Herriot [CHU - HCL], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Functional assay [SDV]Life Sciences [q-bio] Population Immunology Gene Expression lcsh:Medicine chemical and pharmacologic phenomena Proof of Concept Study Monocytes Article Sepsis Enterotoxins 03 medical and health sciences 0302 clinical medicine Immune system medicine Humans education lcsh:Science Aged Cross Infection education.field_of_study Multidisciplinary Tumor Necrosis Factor-alpha Septic shock business.industry Gene Expression Profiling lcsh:R 030208 emergency & critical care medicine HLA-DR Antigens Middle Aged medicine.disease Shock Septic Pathophysiology 030104 developmental biology Female Tumor necrosis factor alpha lcsh:Q business Ex vivo Biomarkers |
| Zdroj: | Scientific Reports Scientific Reports, 2020, 10 (1), pp.16136. ⟨10.1038/s41598-020-73014-2⟩ Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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