Sepsis endotypes identified by host gene expression across global cohorts.

Autor: Chenoweth JG; Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA. jchenoweth@aceso-sepsis.org., Brandsma J; Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Striegel DA; Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Genzor P; Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Chiyka E; Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Blair PW; Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Krishnan S; Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Dogbe E; Laboratory Services Directorate, KATH, Kumasi, Ghana., Boakye I; Research and Development Unit, KATH, Kumasi, Ghana., Fogel GB; Natural Selection, Inc., San Diego, CA, USA., Tsalik EL; Center for Infectious Disease Diagnostics and Innovation, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.; Danaher Diagnostics, Washington, DC., USA., Woods CW; Center for Infectious Disease Diagnostics and Innovation, Department of Medicine, Duke University School of Medicine, Durham, NC, USA., Owusu-Ofori A; Laboratory Services Directorate, KATH, Kumasi, Ghana.; Department of Clinical Microbiology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana., Oppong C; Accident and Emergency Department, KATH, Kumasi, Ghana., Oduro G; Accident and Emergency Department, KATH, Kumasi, Ghana., Vantha T; Takeo Provincial Referral Hospital, Takeo, Cambodia., Letizia AG; Naval Medical Research Unit EURAFCENT Ghana detachment, Accra, Ghana., Beckett CG; Naval Medical Research Command Infectious Diseases Directorate, Silver Spring, MD, USA., Schully KL; Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), Biological Defense Research Directorate, Naval Medical Research Command-Frederick, Ft. Detrick, Maryland, MD, USA., Clark DV; Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
Jazyk: angličtina
Zdroj: Communications medicine [Commun Med (Lond)] 2024 Jun 18; Vol. 4 (1), pp. 120. Date of Electronic Publication: 2024 Jun 18.
DOI: 10.1038/s43856-024-00542-7
Abstrakt: Background: Sepsis from infection is a global health priority and clinical trials have failed to deliver effective therapeutic interventions. To address complicating heterogeneity in sepsis pathobiology, and improve outcomes, promising precision medicine approaches are helping identify disease endotypes, however, they require a more complete definition of sepsis subgroups.
Methods: Here, we use RNA sequencing from peripheral blood to interrogate the host response to sepsis from participants in a global observational study carried out in West Africa, Southeast Asia, and North America (N = 494).
Results: We identify four sepsis subtypes differentiated by 28-day mortality. A low mortality immunocompetent group is specified by features that describe the adaptive immune system. In contrast, the three high mortality groups show elevated clinical severity consistent with multiple organ dysfunction. The immunosuppressed group members show signs of a dysfunctional immune response, the acute-inflammation group is set apart by molecular features of the innate immune response, while the immunometabolic group is characterized by metabolic pathways such as heme biosynthesis.
Conclusions: Our analysis reveals details of molecular endotypes in sepsis that support immunotherapeutic interventions and identifies biomarkers that predict outcomes in these groups.
(© 2024. The Author(s).)
Databáze: MEDLINE
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