Diagnostic performance of fecal eosinophil-derived neurotoxin and lipocalin-2 in pediatric inflammatory bowel disease

Abstract

BACKGROUND: Non-invasive biomarkers for inflammatory bowel disease (IBD) diagnosis in children are needed to reduce dependence on invasive procedures. This study examined fecal eosinophil-derived neurotoxin (fEDN), lipocalin-2 (LCN-2), and calprotectin (FC) as potential non-invasive supportive markers in pediatric IBD. METHODS: This case-control study included 90 participants: 30 IBD patients (12 Crohn's disease, 18 ulcerative colitis), 30 acute diarrhea patients, and 30 healthy controls. Fecal samples were analysed for fEDN, LCN-2, and FC levels (ng/mL) using ELISA. Biomarker levels were correlated with clinical and endoscopic activity scores, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis with pairwise AUC comparisons by DeLong's test. RESULTS: All three biomarkers were significantly elevated in IBD compared to acute diarrhea and healthy controls (p < 0.001). LCN-2 uniquely correlated with disease duration (r = 0.43, p = 0.017) and CRP (r = 0.46, p = 0.011). All markers significantly correlated with the Crohn's Disease Activity Index, with LCN-2 showing the strongest correlation (r = 0.75, p = 0.005). Only FC significantly correlated with the simple endoscopic score (r = 0.63, p = 0.004). For distinguishing IBD from healthy controls, all three markers showed high diagnostic accuracy: calprotectin (AUC = 0.98), fEDN (AUC = 0.95), and LCN-2 (AUC = 0.9), with no statistically significant difference among them (DeLong's test, all p > 0.05). For discriminating IBD from acute diarrhea, FC demonstrated the highest specificity (90%) and overall accuracy (AUC = 0.86), while fEDN performed poorly (AUC = 0.56). All markers showed limited ability to differentiate between IBD subtypes. CONCLUSIONS: In this exploratory study, fEDN, LCN-2, and FC were significantly elevated in pediatric IBD and showed variable but complementary discriminative performance across clinical comparisons, with calprotectin demonstrating the strongest overall accuracy for distinguishing IBD from acute diarrhea. LCN-2 was the only marker that correlated with disease duration, suggesting it may reflect chronic inflammatory processes. These findings support the potential utility of these biomarkers as non-invasive supportive tools in the pre-endoscopic assessment of pediatric IBD; however, formal combined-marker analyses were not performed, and the results require validation in larger prospective multicenter studies before clinical application.