Immunoglobulin G N-glycosylation predicts outcome in sepsis caused by pathogenic Gram-negative bacteria and Gram-positive bacteria: a nested case-control study

BackgroundSepsis remains a critical global health challenge with high mortality. Rapid distinction between Gram-positive and Gram-negative pathogens is critical for empiric antibiotic selection, yet reliable biomarkers for such pathogen stratification are lacking.

Immunoglobulin G (IgG) N-glycosylation modulates inflammatory responses in various diseases, suggesting its potential role in sepsis pathogenesis and prognosis.MethodsIn this nested case-control study, 180 septic patients (100 Gram-negative, 80 Gram-positive) and 100 healthy controls were enrolled. IgG N-glycosylation was analyzed using Hydrophilic interaction chromatography based on ultra-performance liquid chromatography (HILIC-UPLC).

Inflammatory cytokines and clinical parameters were collected. Least absolute shrinkage and selection operator (LASSO) and logistic regression were used to identify glycan biomarkers and construct predictive models for pathogen type and 90-day mortality.

Model performance was evaluated using the area under the receiver operating characteristic curve (AUC).ResultsIn patients with Gram-negative sepsis, levels of 12 glycan peaks (A2B, M5, A2G1, FA2[3]G1, FA2[3]BG1, A2G2, A2BG2, FA2G2, A2G2S1, FA2G2S1, A2G2S2, A2BG2S2) were significantly decreased, while levels of FA1, A2, FA2, FA2B, FA2BG2, and FA2FG2S1 were increased (all P < 0.05, q < 0.05), compared to patients with Gram-positive sepsis.