Characterization of sepsis inflammatory endotypes using circulatory proteins in patients with severe infection: a prospective cohort study.
Endotypes
Hyperinflammation
Proteomics
Sepsis
Severe infections
Journal
BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551
Informations de publication
Date de publication:
08 Oct 2022
08 Oct 2022
Historique:
received:
08
04
2022
accepted:
26
09
2022
entrez:
8
10
2022
pubmed:
9
10
2022
medline:
12
10
2022
Statut:
epublish
Résumé
Sepsis is a heterogeneous syndrome due to a variable range of dysregulated processes in the host immune response. Efforts are made to stratify patients for personalized immune-based treatments and better prognostic prediction. Using gene expression data, different inflammatory profiles have been identified. However, it remains unknown whether these endotypes mirror inflammatory proteome profiling, which would be more feasible to assess in clinical practice. We aim to identify different inflammatory endotypes based on circulating proteins in a cohort of moderately ill patients with severe infection (Sepsis-2 criteria). In this prospective study, 92 inflammatory plasma markers were profiled using a targeted proteome platform and compared between patients with severe infection (Sepsis-2 criteria) and healthy controls. To identify endotypes with different inflammatory profiles, we performed hierarchical clustering of patients based on the differentially expressed proteins, followed by clinical and demographic characterization of the observed endotypes. In a cohort of 167 patients with severe infection and 192 healthy individuals, we found 62 differentially expressed proteins. Inflammatory proteins such as TNFSF14, OSM, CCL23, IL-6, and HGF were upregulated, while TRANCE, DNER and SCF were downregulated in patients. Unsupervised clustering identified two different inflammatory profiles. One endotype showed significantly higher inflammatory protein abundance, and patients with this endotype were older and showed lower lymphocyte counts compared to the low inflammatory endotype. By identifying endotypes based on inflammatory proteins in moderately ill patients with severe infection, our study suggests that inflammatory proteome profiling can be useful for patient stratification.
Sections du résumé
BACKGROUND
BACKGROUND
Sepsis is a heterogeneous syndrome due to a variable range of dysregulated processes in the host immune response. Efforts are made to stratify patients for personalized immune-based treatments and better prognostic prediction. Using gene expression data, different inflammatory profiles have been identified. However, it remains unknown whether these endotypes mirror inflammatory proteome profiling, which would be more feasible to assess in clinical practice. We aim to identify different inflammatory endotypes based on circulating proteins in a cohort of moderately ill patients with severe infection (Sepsis-2 criteria).
METHODS
METHODS
In this prospective study, 92 inflammatory plasma markers were profiled using a targeted proteome platform and compared between patients with severe infection (Sepsis-2 criteria) and healthy controls. To identify endotypes with different inflammatory profiles, we performed hierarchical clustering of patients based on the differentially expressed proteins, followed by clinical and demographic characterization of the observed endotypes.
RESULTS
RESULTS
In a cohort of 167 patients with severe infection and 192 healthy individuals, we found 62 differentially expressed proteins. Inflammatory proteins such as TNFSF14, OSM, CCL23, IL-6, and HGF were upregulated, while TRANCE, DNER and SCF were downregulated in patients. Unsupervised clustering identified two different inflammatory profiles. One endotype showed significantly higher inflammatory protein abundance, and patients with this endotype were older and showed lower lymphocyte counts compared to the low inflammatory endotype.
CONCLUSIONS
CONCLUSIONS
By identifying endotypes based on inflammatory proteins in moderately ill patients with severe infection, our study suggests that inflammatory proteome profiling can be useful for patient stratification.
Identifiants
pubmed: 36209073
doi: 10.1186/s12879-022-07761-0
pii: 10.1186/s12879-022-07761-0
pmc: PMC9547371
doi:
Substances chimiques
Biomarkers
0
Interleukin-6
0
Proteome
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
778Subventions
Organisme : European Society of Clinical Microbiology and Infectious Diseases
ID : 2017
Organisme : Radboud Universitair Medisch Centrum
ID : Hypatia Grant 2018
Organisme : ZonMw
ID : ZonMw COVID-19
Pays : Netherlands
Organisme : Romanian Ministry of European Funds
ID : FUSE
Organisme : European Research Council
ID : 833247
Pays : International
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : Spinoza Grant
Informations de copyright
© 2022. The Author(s).
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