N-glycosylation of Immunoglobulin G as a Predictor of Outcomes in Sepsis

Overview

This study identifies IgG N-glycosylation profiles as biomarkers for distinguishing between Gram-negative and Gram-positive sepsis.

Background

Sepsis is a significant global health issue characterized by a dysregulated response to infection, leading to high mortality rates. Accurate differentiation between Gram-negative and Gram-positive bacterial infections is crucial for appropriate antibiotic therapy, yet reliable biomarkers for this distinction are currently lacking. The study explores the potential of IgG N-glycosylation as a biomarker for sepsis outcomes.

Data Highlights

Key Findings

• 12 glycan peaks were significantly decreased in Gram-negative sepsis compared to Gram-positive sepsis.
• Glycan FA2 was identified as a strong independent predictor of 90-day mortality (AUC = 0.792).
• The combined model of FA2 and SOFA score improved predictive accuracy for mortality (AUC = 0.820).
• Significant differences in fucosylation, sialylation, agalactosylation, and digalactosylation levels were observed between septic survivors and non-survivors.
• The model incorporating glycan peaks and clinical markers showed excellent discrimination (AUC = 0.931 in training, 0.917 in validation).

Clinical Implications

IgG N-glycosylation profiles may serve as biomarkers for differentiating between Gram-negative and Gram-positive sepsis.

Conclusion

IgG N-glycosylation serves as a biomarker for pathogen differentiation and mortality prediction in sepsis.

Related Resources & Content

1. Frontiers in Endocrinology, 2026 -- Association of TyG index with sepsis incidence and mortality: a prospective study with diabetes stratification
2. Infection, 2024 -- Frequency and Risk Factors for Complications in Bloodstream Infections Caused by Gram-Negative Bacteria
3. Infection, 2024 -- Reduced CCL5 Gene Expression and Serum Levels in Severe Invasive Group A Streptococcal Infections
4. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026 | SCCM
5. Brain — Comprehensive Analysis of Antibody Responses to Glycolipids in Individuals Diagnosed with Guillain-Barré Syndrome
6. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026 | SCCM
7. Executive Summary: Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026 - PubMed
8. Biomarkers to guide sepsis management | Annals of Intensive Care | Springer Nature Link
9. Frontiers | Immunoglobulin G N-Glycome as a biomarker of mortality risk in Escherichia coli induced sepsis
10. Reprogramming of the Sepsis N-Glycoproteome Illuminates a Functional Dissociation between Protein Abundance and Glycosylation in Immunothrombosis | medRxiv
11. Fucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study | Nature Communications
12. IgG Glycosylation: Biomarker, Functional Modulator, and Structural Component - PubMed
13. A systematic review of protein post-translational modifications in sepsis - PMC