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

Abstract

BackgroundPatients 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.ObjectiveThis observational study aimed to assess the predictive role of neutrophils according to tissue localization and intestinal barrier protein expression in IBD.MethodsIBD 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).ResultsOf 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.ConclusionThis 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.