P0751Epithelial Lipocalin-2 Mirrors Mucosal Inflammation Severity in Inflammatory Bowel Disease

Abstract Background Lipocalin-2 (LCN2) has been proposed as a biomarker for inflammatory bowel disease (IBD). However, we came across transcriptome datasets showing contradictory results when we expanded our research on LCN2 in intestinal inflammation. Methods Associations between mucosal LCN2 expression and inflammation severity were analyzed using transcriptomic data from patients with Crohn’s disease (CD) and ulcerative colitis. LCN2 and S100A8/9 mRNA expression were compared in ileal and colonic mucosa from IBD patients and controls. Publicly available single-cell RNA sequencing data and immunofluorescence staining of terminal ileum biopsies from independent inflammatory cases were used to validate RNA-level findings. We also assessed the diagnostic potential of fecal lipocalin-2 (FLCN2) and fecal calprotectin (FCAL) in 87 patients with CD and healthy controls (n = 22) with Simplified Endoscopic Scores for Crohn’s Disease (SES-CD) ranging from 0 to 27 scores. Results LCN2 demonstrated greater accuracy in detecting low-grade inflammation than S100A8/9. LCN2 expression increased from mild to moderate disease but declined at high SES-CD. Elevated immune cell infiltration during moderate to severe inflammation corresponded to a larger fraction of cells expressing little or no LCN2. Protein-level analysis localized LCN2 primarily to intestinal epithelial cells (IECs), whose abundance and LCN2 levels diminished with increasing disease severity. In our external validation cohort, FLCN2 exhibited diagnostic sensitivity comparable to FCAL. Conclusion Persistent LCN2 overexpression in IECs, even after endoscopic and histological healing, indicates dysregulated epithelial responses. LCN2 thus represents a promising biomarker of disease activity and a potential therapeutic target in IBD. Conflict of interest: Ms. Li, Qing: No conflict of interest Gao, Xiang: No conflict of interest Chao, Kang: No conflict of interest