Immune Subtypes in Sepsis: A Retrospective Cohort Study Utilizing Clustering Methodology

Area of Science:

• Immunology
• Critical Care Medicine
• Biostatistics

Background:

• Sepsis is a complex clinical syndrome with significant heterogeneity.
• Identifying distinct patient phenotypes is crucial for targeted therapies and improved outcomes.
• Current understanding of sepsis subtypes requires further refinement for personalized medicine.

Purpose of the Study:

• To employ clustering analysis to delineate immune subtypes within sepsis patient cohorts.
• To investigate the clinical relevance and prognostic implications of identified sepsis immune subtypes.
• To establish a foundation for tailored therapeutic interventions in sepsis management.

Main Methods:

• Utilized K-means clustering on demographic, clinical, lymphocyte subset, and cytokine data from 236 sepsis patients (Sepsis 3.0 criteria).
• Analyzed immune and inflammatory markers including C-reactive protein (CRP), white blood cell (WBC) counts, T cells, NK cells, B cells, IL-6, IL-8, and IL-10.
• Assessed 28-day mortality risk and survival rates using hazard ratios and Kaplan-Meier curves.

Main Results:

• Identified three distinct immune subtypes: high immune activation (Cluster 1), moderate immune activation (Cluster 2), and high inflammation/immune suppression (Cluster 3).
• Cluster 3 exhibited significantly higher 28-day mortality (HR=21.65, p<0.001) compared to Cluster 1.
• Kaplan-Meier analysis revealed significantly different survival rates across the three subtypes (p<0.0001), with Cluster 3 having the lowest survival.

Conclusions:

• Three distinct immune subtypes of sepsis patients are identifiable and significantly associated with clinical outcomes.
• The identified immune subtypes offer a basis for stratifying sepsis patients.
• These findings support the development of personalized treatment strategies to enhance sepsis patient care and prognosis.