Circulating DNA and Neutrophil-Derived Biomarkers in Neonatal Sepsis

Area of Science:

• Neonatal immunology
• Infectious diseases
• Biomarker discovery

Background:

• Neutrophil extracellular traps (NETs) are crucial in innate immunity during sepsis.
• The diagnostic utility of NET-associated biomarkers in neonatal sepsis remains uncertain.
• Neonatal immune responses may differ significantly from adult patterns.

Purpose of the Study:

• To evaluate if circulating NET-associated biomarkers can distinguish septic from non-infected neonates.
• To compare the diagnostic performance of NET biomarkers with established markers like CRP and IL-6.
• To investigate the correlation between NET markers and neutrophil degranulation in neonatal sepsis.

Main Methods:

• Prospective observational study of 96 neonates with suspected infection (36 sepsis, 60 controls).
• Measurement of serum cell-free DNA (cfDNA), myeloperoxidase-DNA complexes (MPO-DNA), neutrophil elastase-DNA complexes (NE-DNA), citrullinated histone H3 (H3cit), CRP, and IL-6.
• Receiver operating characteristic (ROC) analysis to assess diagnostic performance.

Main Results:

• CRP (AUC 0.75) and IL-6 (AUC 0.73) demonstrated the best diagnostic performance.
• cfDNA showed moderate discrimination (AUC 0.72) but was transiently elevated.
• MPO-DNA, NE-DNA, and H3cit showed no significant diagnostic value (AUCs ≤ 0.47).
• MPO-DNA and NE-DNA correlated with immature-to-total neutrophil ratio, indicating degranulation rather than NET formation.

Conclusions:

• NET-associated biomarkers do not enhance diagnostic accuracy for neonatal sepsis beyond CRP and IL-6.
• Findings suggest that neonatal innate immune responses to sepsis differ from adult patterns.
• Further research is needed to understand unique neonatal immune mechanisms in sepsis.