P0159Altered Expression of Occludin and Claudin-1 in IBD Correlates with Disease Activity, Predicts Long-term Outcomes, and Is Restored by Effective Biologic Therapy

Background Compromise of tight junction (TJ) integrity is a key feature of gut barrier dysfunction in IBD, contributing to local mucosal injury and systemic inflammation1,2. This study aimed to evaluate the expression of two basic TJ proteins—occludin and claudin-1—in intestinal mucosa and investigate their association with disease characteristics and clinical outcomes. Methods We conducted a hybrid cohort study combining analysis of retrospective archived colonic or ileal biopsies with prospective clinical and endoscopic follow-up (FUP), including paired biopsies (obtained at > 6 months). Immunohistochemistry (IHC) was performed, and protein expression in crypts (CR) and surface epithelium (SE) was assessed using a semi-quantitative H-score. Results A total of 192 patients (CD/UC: 93/99; male: 57.8%; median age: 40 years; median FUP: 51 months) were recruited along with 61 healthy controls (HC). Paired biopsies were available in 102 patients. Patients with active UC (FMS>6) exhibited increased cytoplasmic occludin expression in both SE (p = 0.013) and CR (p = 0.046) compared with HC. Similarly, patients with active CD (CDAI>150) showed increased cytoplasmic occludin in SE (p = 0.01) and CR (p = 0.045), along with elevated claudin-1 levels in CR (p = 0.019). In contrast, HC samples displayed predominantly membranous localization of both proteins. Cytoplasmic expression of occludin in CR correlated positively with disease activity markers, including CDAI (p = 0.004) and HBI (p = 0.02) in CD and the FMS (p < 0.001) in UC, with systemic inflammation indices, such as CRP (p = 0.001), with endoscopic activity (SES-CD, p = 0.009; Mayo endoscopic score, p = 0.003), and with histological activity (Nancy index, p = 0.006). Patients who underwent an IBD-related surgery at FUP (21.7%) showed significantly higher baseline levels of occludin in the CR (p = 0.036) compared to those who remained free of surgery. Furthermore, lower baseline occludin levels in the CR were associated with increased surgery-free survival (Kaplan-Meier analysis; p = 0.03) (Figure ID-IE). In follow-up biopsies, a significant restoration of both occludin (p = 0.001) and claudin-1 (p = 0.002) expression was evident in the CR. Patients who received biologic agents during the FUP (45.3%) achieved a more profound decrease in cytoplasmic occludin (-42.6 ± 72 vs. -14.2 ± 48; p = 0.04) and claudin-1 levels (-53.6 ± 68 vs. -5.4 ± 40; p = 0.002) in the CR compared to bio-naïve patients. Conclusion Active inflammation in IBD is associated with marked disruption of occludin and claudin-1 expression. TJ impairment appears to carry prognostic value for long-term disease outcomes, while effective treatment—particularly with biologic agents—restores their expression. References: 1. Assimakopoulos SF, Triantos C, Maroulis I, Gogos C. The Role of the Gut Barrier Function in Health and Disease. Gastroenterology Res. 2018;11(4):261-263. 2. Landy J, Ronde E, English N, et al. Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. World J Gastroenterol. 2016;22(11):3117-3126. Conflict of interest: Tsounis, Efthymios: No conflicts Geramoutsou, Christina: No potential CoI Pastras, Pl: No conflicts Aggeletopoulou, Ioanna: No conflicts Bosgana, Pinelopi: No conflicts Lourida, Theoni: No conflicts Diamantopoulou, Georgia: No conflicts Zolota, Vasiliki: No conflicts Assimakopoulos, Stelios F: No Conflicts Bravou, Vasiliki: No conflicts Thomopoulos, Konstantinos: No conflicts Theocharis, Georgios: No conflicts Prof. Triantos, Christos: No potential CoI