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Updated: Dec 18, 2025
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A Data-Driven Approach to Quantifying Immune States in Sepsis
Published on: February 7, 2025
167
Sepsis endotypes identified by host gene expression across global cohorts
Josh G Chenoweth1, Joost Brandsma2, Deborah A Striegel2
1Austere 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.
Communications Medicine
|June 18, 2024
Summary
Researchers identified four sepsis subtypes based on host immune responses and mortality. This discovery aids in developing precision medicine and targeted immunotherapies for sepsis patients.
Area of Science:
- Genomics and transcriptomics
- Immunology
- Precision medicine
Background:
- Sepsis is a global health priority with limited therapeutic options.
- Heterogeneity in sepsis pathobiology complicates treatment.
- Precision medicine requires better definition of sepsis subgroups.
Purpose of the Study:
- To define sepsis subgroups using host response.
- To identify molecular endotypes for improved outcomes.
- To discover biomarkers for sepsis patient stratification.
Main Methods:
- RNA sequencing of peripheral blood from 494 sepsis patients.
- Global observational study across West Africa, Southeast Asia, and North America.
- Analysis of host response to differentiate sepsis subtypes.
Main Results:
- Four sepsis subtypes identified, differentiated by 28-day mortality.
- A low-mortality immunocompetent subtype with adaptive immune features.
- Three high-mortality subtypes: immunosuppressed, acute-inflammation, and immunometabolic, with distinct molecular profiles.
Conclusions:
- Sepsis molecular endotypes provide targets for immunotherapeutic interventions.
- Biomarkers identified can predict patient outcomes.
- This research advances precision medicine approaches for sepsis.
