Epithelial neutrophil localization and tight junction Claudin-2 expression are innovative outcome predictors in inflammatory bowel disease

Background: Patients with inflammatory bowel disease (IBD) in clinical and endoscopic remission may still experience disease relapse. Therefore, there is a need to identify outcome predictors. Recently, the role of neutrophils in predicting outcomes in ulcerative colitis (UC) has been highlighted. Furthermore, the impairment of intestinal barrier plays a key role in forecasting disease outcomes in IBD. Objective: This observational study aimed to assess the predictive role of neutrophils according to tissue localization and intestinal barrier protein expression in IBD. Methods: IBD patients in clinical remission who underwent colonoscopy between January 2020 and June 2022 at two tertiary referral centres were enrolled. Patients with Mayo Endoscopic Score ≤1 (UC) and Simple Endoscopic Score ≤6 (Crohn's disease) were included. Histological activity was assessed using validated scores. Experienced pathologists evaluated neutrophil localization in the epithelium and lamina propria and immunohistochemical expression of Claudin-2 and junctional adhesion molecule A (JAM-A). Results: Of 60 UC and 76 CD patients, 59.7% had histological activity. 25.8% of patients developed an adverse outcome within 12 months. Neutrophils in the epithelium predicted adverse outcomes for UC (hazard ratio [HR] 5.198, p = 0.01) and CD (HR 4.377, p = 0.03) patients in endoscopic remission. Claudin-2 expression correlated with endoscopic and histological activity and predicted outcomes in UC. Similar results were found for JAM-A in CD despite this protein showing less specificity as a barrier predictor of outcome. Conclusion: This study highlights the potential role of epithelial neutrophil localization and Claudin-2 ‘leaky gut’ expression as tools for predicting IBD outcomes and guiding further patient-tailored therapy.