P431 Assessing intestinal barrier healing by fusing ultra-high magnification endoscope and automated spatial multispectral imaging analysis in PSC-colitis patients

Abstract

Abstract Background PSC colitis is associated with an increased risk of colorectal carcinoma. Endoscopic monitoring is crucial since endoscopic and histological activity can persist in PSC even during clinical remission. Recent evidence suggests that the presence of barrier dysfunction may predict relapse in quiescent patients. This study aims to assess mucosal and barrier healing in quiescent PSC colitis and evaluate the potential to predict outcomes by combining an ultra-high magnification endocytoscope (ECS) with intestinal barrier protein markers. Methods 23 PSC-colitis patients in clinical remission requiring surveillance colonoscopy were prospectively enrolled. Ileal and colonic mucosa were assessed with high definition, virtual chromoendoscopy and ultra-high magnification ECS. Endoscopic remission was defined as MES ≤1, UCEIS≤1, PICaSSO≤3, while histological remission was defined as RHI≤3 without lamina propria or epithelial neutrophils, NHI ≤1 and PHRI=0. A novel ECS score was developed to assess ileal and colonic intestinal barrier (Table 1). The expression of tight junction proteins (Claudin-2, Occludin, and JAM-A) was evaluated through immunohistochemistry and multiplex immunofluorescence, and it was quantified as cell density and mean expression using the automated inForm® Akoya Biosciences digital multiplex platform. The occurrence of significant adverse outcomes (steroid use, flare-ups, hospitalization, colectomy) was evaluated over a 12-month follow-up period. Results Of 18 patients in endoscopic remission, 12 and 13 were in histological remission according to RHI and NHI, respectively. The ECS score correlated moderately with endoscopic score (r=0.57 for MES, r=0.44 for UCEIS and r=0.54 for PICaSSO) and strongly with histological scores (r=0.56 for RHI, r=0.61 for NHI and r=0.62 for PHRI), especially in the right colon. Only 5 patients experienced adverse outcomes. Notably, barrier healing, as indicated by an ECS score<3 in the ileum and <5 in the colon, was significantly associated with better outcomes. The three barrier proteins showed a distinct mucosal localisation in both ileum and colon, with higher cell density of Occludin and Claudin-2 in the epithelium, while higher JAM-A cell density in the lamina propria. The combined assessment of the intestinal barrier by ECS and Claudin-2 cell density significantly predicted outcomes in both colon and ileum (p=0.02 and p=0.04, respectively). Conclusion ECS combined with automated multispectral imaging analysis of intestinal barrier integrity is an innovative tool to assess barrier healing precisely and predicts significant adverse outcomes in PSC colitis patients in clinical, endoscopic, and histological remission.