D1.513 - Reduced Expression of PDCD4 on CD14+ Monocytes Correlates with Inflammatory Severity in Neonatal Sepsis: A Pilot Study

Neonatal sepsis is characterized by immune immaturity and dysregulated inflammation. Neonates rely predominantly on innate immune responses, with monocytes playing a central role in regulating systemic inflammation. While PDCD4 has been implicated in adult immune signaling, its role in neonatal sepsis remains poorly understood. This pilot study aimed to characterize PDCD4 expression on CD14+ monocytes in septic neonates and evaluate its association with systemic inflammatory markers to provide insights into inflammatory burden and innate immune status.

Peripheral blood was collected from neonates with clinical or culture-proven sepsis (n=16) and non-septic controls (n=4, limited by ethical constraints of healthy neonatal sampling). Flow cytometry quantified PDCD4 expression on CD14⁺ monocytes. Serum C-reactive protein (CRP) and procalcitonin (PCT) were measured concurrently. Group comparisons utilized the Mann-Whitney U test, and correlations were assessed via Spearman’s rank analysis. Exploratory ROC analysis evaluated discriminatory potential. Data were analyzed using two-tailed tests with P<0.05 considered significant.

Flow cytometric analysis demonstrated significantly lower PDCD4 expression on CD14⁺ monocytes in septic neonates compared with controls (P<0.05). Decreased PDCD4 expression showed a strong inverse correlation with increased inflammatory burden: CRP (r=-0.8105, P<0.05) and PCT (r=-0.6136, P<0.05). In this small cohort, exploratory ROC analysis yielded an area under the curve (AUC) of 0.969; however, given the limited control size, this high discriminatory metric requires cautious interpretation.

This pilot study identifies PDCD4 downregulation as a distinct immunological marker associated with inflammatory severity in neonatal sepsis. Rather than reflecting inflammation alone, PDCD4 may indicate altered innate immune regulatory capacity. Despite sample size constraints, these findings support its preliminary feasibility as a novel biomarker for precision immune stratification, highlighting the critical need for further mechanistic studies to elucidate the specific immunoregulatory role of PDCD4 in neonatal sepsis.