Single-cell multi-omic landscape reveals anatomical-specific immune features in adult and pediatric sepsis.

Summary

This large human cohort integrates single-cell transcriptomics, immune receptor sequencing, CITE-seq, bulk RNA-seq, and proteomics to show that the anatomical source of infection imprints distinct immune programs in sepsis across adults and children, including an NR4A2-linked signature. The dataset provides a reference map for site-specific immune states and candidate biomarkers.

Key Findings

• Integrated single-cell and plasma multi-omics in 281 individuals revealed infection-site-specific immune programs.
• An NR4A2-associated immune signature was identified within sepsis immune states.
• Adult and pediatric sepsis shared core features but exhibited source- and age-specific immune differences.

Clinical Implications

Supports risk stratification and targeted diagnostics by infection source; informs trial design using immune endotypes and may guide precision immunomodulation.

Limitations

• Abstract suggests cross-sectional profiling; causal inferences are limited
• Details of external validation and clinical utility thresholds are not provided in the abstract

Future Directions

Prospective validation of site-specific immune endotypes to guide targeted therapies and development of clinically deployable biomarker panels.