Longitudinal blood transcriptome profiling reveals immune dynamics in sepsis.

Area of Science:

• * Molecular biology and immunology.
• * Computational biology and bioinformatics.
• * Clinical research in critical care medicine.

Background:

• * Sepsis is a life-threatening condition with a heterogeneous host response to infection.
• * Transcriptomic profiling can reveal immune gene expression patterns for patient stratification.
• * Identifying specific transcriptomic signatures is crucial for understanding sepsis heterogeneity.

Purpose of the Study:

• * To identify transcriptomic signatures indicative of sepsis or septic shock.
• * To correlate these signatures with disease severity and patient outcomes.
• * To explore the temporal dynamics of the host immune response in sepsis.

Main Methods:

• * Enrollment of 11 adult patients with sepsis or septic shock.
• * Serial whole-blood sample collection on days 1, 3, and 7.
• * RNA sequencing and principal component analysis (PCA) to derive a gene signature.
• * Validation using external bulk and single-cell RNA-seq datasets.

Main Results:

• * PCA revealed PC1 as the primary variation axis, separating samples by sepsis severity and time.
• * Three transcriptomic subgroups were identified based on distinct gene expression patterns.
• * Enrichment scores correlated with sepsis severity, declined over time, and predicted 28-day mortality.
• * Functional analysis highlighted neutrophil-associated pathways.

Conclusions:

• * A neutrophil-driven transcriptomic signature associated with sepsis severity and immune dynamics was identified.
• * Longitudinal transcriptomic profiling offers insights into the evolving host immune response in sepsis.
• * This signature may aid in patient stratification and understanding sepsis heterogeneity.