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Updated: Mar 13, 2026
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Plasma Proteomic Signatures of Pediatric Sepsis Reveal Persistent Inflammation and Phase-Specific Biomarkers
Fahd Alhamdan1,2,3, Yi-Cheng Sin4, Erik Malm1
1Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division Boston Children's Hospital Boston Massachusetts USA.
Insights
Pediatric sepsis involves complex immune and vascular changes. This study identified key protein biomarkers and distinct complement pathway activity in children, offering insights for diagnosis and treatment.
Area of Science:
- Immunology
- Proteomics
- Pediatric Critical Care Medicine
Background:
- Sepsis is a major cause of death in children, but its molecular basis is unclear.
- Understanding pediatric sepsis is crucial for improving outcomes.
Purpose of the Study:
- To investigate the plasma proteome and cytokine profiles in pediatric sepsis.
- To identify biomarkers for sepsis diagnosis and differentiate it from sterile inflammation.
- To explore age-specific differences in immune response compared to adults.
Main Methods:
- Plasma proteomics and cytokine profiling using mass spectrometry.
- Analysis of patients in acute phase (AP) and recovery phase (RP) vs. surgical controls.
- Machine learning for biomarker identification and comparison with adult and sterile inflammation cohorts.
Main Results:
- Identified 41 differentially abundant proteins in AP vs. control, with persistent changes in RP.
- Sustained inflammatory and complement activation pathways in both AP and RP.
- Highlighted complement components (C9, C1R) and LRG1 as AP biomarkers; S100A9 as an RP marker.
- Observed enhanced alternative complement pathway activity in pediatric sepsis versus classical pathway in adults.
- Differentiated sepsis from sterile inflammation by immune response patterns (adaptive vs. innate).
Conclusions:
- Pediatric sepsis exhibits dynamic proteomic changes involving immune and vascular systems.
- Identified novel biomarkers distinguishing sepsis from sterile inflammation.
- Revealed age-specific complement pathway activation patterns with therapeutic implications.
Abstract:
Sepsis remains a leading cause of pediatric morbidity and mortality, yet its molecular underpinnings are poorly understood. Here, we performed mass spectrometry-based plasma proteomics and cytokine profiling in pediatric sepsis patients at the acute phase (AP) and recovery phase (RP), alongside preoperative surgical controls. In AP vs. control, we identified 41 differentially abundant (DA) proteins, including acute-phase reactants and complement factors, with persistent but attenuated expression in RP. Pathway analysis revealed sustained enrichment in inflammatory and complement activation processes during both AP and RP, with partial restoration of immune surveillance and vascular homeostasis in recovery. Machine learning highlighted complement components (C9, C1R) and LRG1 as candidate AP biomarkers, and S100A9 as an RP-associated marker. Comparative analysis with adult sepsis proteomes uncovered age-specific complement activation patterns: adults displayed higher classical pathway activity, whereas pediatric patients exhibited enhanced alternative pathway activity. Cytokine profiling confirmed sustained immune activation and endothelial perturbation across sepsis phases. We also compared the sepsis cohort with the sterile inflammation (SI) cohort, which revealed distinct adaptive immune enrichment in sepsis while innate immune predominance in SI, enabling the identification of potential sepsis-specific protein signatures. Together, these findings delineate the dynamic immune and vascular proteomic landscape of pediatric sepsis, reveal biomarkers distinguishing sepsis from sterile inflammation, and highlight age-related complement pathway differences with potential therapeutic implications. Trial Registration: ClinicalTrials.gov: NCT04103268, NCT04299828.
