Monocyte microRNA signatures in late-onset neonatal sepsis
Abstract Purpose: Neonatal late-onset sepsis (LOS) remains a major cause of neonatal morbidity and its non-specific presentation challenges early diagnosis. MicroRNAs (miRNAs) are promising biomarkers, but unbiased next-generation sequencing (NGS) of monocyte-specific miRNA has not been applied to neonatal LOS. We aimed to identify the monocyte-specific miRNA expression profile in neonatal LOS and its associations with the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). Methods: In a prospective study at the University General Hospital of Patras, 30 samples from 15 neonates with LOS and 8 healthy controls were analyzed. Monocyte miRNA expression was characterized by NGS pre and post antimicrobial therapy in cases and controls. Predicted target genes of the major candidate miRNAs were evaluated by RT-qPCR in an independent cohort. Clinical severity was assessed using NLR and SII. Results: Hsa-miR-6743-3p was significantly upregulated on day 0 and returned to control levels by day 2. Four additional miRNAs (hsa-miR-7108-5p, hsa-miR-3940-5p, hsa-miR-6851-3p and hsa-miR-1909-3p) exhibited a consistent trend toward upregulation in acute LOS. NLR, but not SII, was significantly elevated at diagnosis and showed excellent diagnostic performance (AUC 0.958), normalizing by day 2. Hsa-miR-7108-5p correlated positively with NLR on day 0. In the RT-qPCR cohort, its predicted target DRAM2, was reduced on day 0 and partially recovered by day 2. Conclusion: Monocyte miRNA profiling identified transient alterations in neonatal LOS that parallel clinical severity, while NLR showed high discriminatory performance. These exploratory findings warrant validation in larger cohorts to verify monocyte miRNAs as potential biomarkers of neonatal LOS.