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

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

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
30 09 2020
Historique:
received: 16 09 2019
accepted: 26 08 2020
entrez: 1 10 2020
pubmed: 2 10 2020
medline: 20 1 2021
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41598-020-73014-2 PMID: 32999313 PMC: PMC7527338
pubmed: 32999313
doi: 10.1038/s41598-020-73014-2
pii: 10.1038/s41598-020-73014-2
pmc: PMC7527338
doi:

Substances chimiques

Biomarkers 0
Enterotoxins 0
HLA-DR Antigens 0
Lipopolysaccharides 0
TNF protein, human 0
Tumor Necrosis Factor-alpha 0
enterotoxin B, staphylococcal 39424-53-8

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

16136

Subventions

Organisme : Marie Curie
ID : 676129
Pays : United Kingdom

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Auteurs

Chloé Albert Vega (C)

Laboratoire Commun de Recherche Hospices Civils de Lyon-bioMérieux, Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Bâtiment 3F, Pierre-Bénite, 69495, Lyon, France. chloe.albertvega@gmail.com.
Open Innovation and Partnerships Department, bioMérieux S.A., Marcy l'Étoile, France. chloe.albertvega@gmail.com.

Guy Oriol (G)

Laboratoire Commun de Recherche Hospices Civils de Lyon-bioMérieux, Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Bâtiment 3F, Pierre-Bénite, 69495, Lyon, France.
Open Innovation and Partnerships Department, bioMérieux S.A., Marcy l'Étoile, France.

François Bartolo (F)

Laboratoire Commun de Recherche Hospices Civils de Lyon-bioMérieux, Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Bâtiment 3F, Pierre-Bénite, 69495, Lyon, France.
Soladis, Lyon, France.

Jonathan Lopez (J)

Hospices Civils de Lyon - Plateforme de Recherche de Transfert en Oncologie, Centre Hospitalier Lyon Sud, Pierre-Bénite, 69495, Lyon, France.

Alexandre Pachot (A)

Open Innovation and Partnerships Department, bioMérieux S.A., Marcy l'Étoile, France.

Thomas Rimmelé (T)

EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University-bioMérieux-Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, France.
Anesthesia and Critical Care Medicine Department, Hôpital Edouard Herriot, Hospices Civils de Lyon, 69437, Lyon, France.

Fabienne Venet (F)

EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University-bioMérieux-Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, France.
Immunology Laboratory, Hôpital Edouard Herriot, Hospices Civils de Lyon, 69437, Lyon, France.

Véronique Leray (V)

Anesthesia and Critical Care Medicine Department, Hôpital Edouard Herriot, Hospices Civils de Lyon, 69437, Lyon, France.

Guillaume Monneret (G)

EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University-bioMérieux-Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, France.
Immunology Laboratory, Hôpital Edouard Herriot, Hospices Civils de Lyon, 69437, Lyon, France.

Benjamin Delwarde (B)

Anesthesia and Critical Care Medicine Department, Hôpital Edouard Herriot, Hospices Civils de Lyon, 69437, Lyon, France.

Karen Brengel-Pesce (K)

Laboratoire Commun de Recherche Hospices Civils de Lyon-bioMérieux, Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Bâtiment 3F, Pierre-Bénite, 69495, Lyon, France.
Open Innovation and Partnerships Department, bioMérieux S.A., Marcy l'Étoile, France.

Julien Textoris (J)

Open Innovation and Partnerships Department, bioMérieux S.A., Marcy l'Étoile, France.
EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University-bioMérieux-Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, France.
Anesthesia and Critical Care Medicine Department, Hôpital Edouard Herriot, Hospices Civils de Lyon, 69437, Lyon, France.

François Mallet (F)

Laboratoire Commun de Recherche Hospices Civils de Lyon-bioMérieux, Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Bâtiment 3F, Pierre-Bénite, 69495, Lyon, France.
Open Innovation and Partnerships Department, bioMérieux S.A., Marcy l'Étoile, France.
EA 7426 Pathophysiology of Injury-Induced Immunosuppression, PI3, Claude Bernard Lyon 1 University-bioMérieux-Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, France.

Sophie Trouillet-Assant (S)

Laboratoire Commun de Recherche Hospices Civils de Lyon-bioMérieux, Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Bâtiment 3F, Pierre-Bénite, 69495, Lyon, France.
CIRI, INSERM U1111, CNRS 5308, ENS, UCBL, Faculté de Médecine Lyon Est, Virpath - Université Lyon, 7 rue Guillaume Paradin, 69372, Lyon Cedex 08, France.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Deciphering heterogeneity of septic shock...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Deciphering heterogeneity of septic shock...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie iatrogène › Infection croisée › Deciphering heterogeneity of septic shock...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Entérotoxines › Deciphering heterogeneity of septic shock...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Deciphering heterogeneity of septic shock...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Deciphering heterogeneity of septic shock...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes HLA › Antigènes HLA-D › Antigènes HLA-DR › Deciphering heterogeneity of septic shock...
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