P060 Restoration of occludin and claudin-1 expression in patients with Crohn’s disease receiving anti-TNF treatment.

Abstract

Background Occludin and claudin-1 are integral components of tight junctions (TJs) that contribute to intestinal barrier integrity. The aim of this study was to prospectively evaluate the expression of occludin and claudin-1 in the intestinal mucosa of patients with Crohn’s disease (CD) undergoing treatment with tumor necrosis factor (TNF) inhibitors. Methods Clinical assessment, laboratory testing, and colonoscopy were performed on all participants prior to receiving anti-TNF therapy. Colonic or ileal biopsies were obtained from the affected intestinal areas. A follow-up exam and colonoscopy were performed at least 6 months after the start of anti-TNF therapy, and paired biopsies were obtained from the initially affected segments. The expression of the TJ proteins was evaluated by immunohistochemistry (IHC). Results In this prospective observational study, 21 consecutive patients with active CD [median age 32.5 years (IQR: 18.5-51), 66.7% male] and 10 healthy controls [36 years (IQR: 29-58), 60% male] were enrolled. Patients with CD received treatment with TNF inhibitors (infliximab, adalimumab, and certolizumab: 61.9%, 33.3%, and 4.8%, respectively), according to current guidelines, and a follow-up examination was conducted after a median period of 25 months (IQR: 9.5-66). Before treatment administration, patients with active CD exhibited an increased expression of both occludin [2 (IQR: 1.75-2.75) vs. 1.5 (IQR: 0-1.75); p = 0.032] and claudin-1 [2.5 (IQR: 2-3) vs. 1 (IQR: 0.75-2); p = 0.01] in comparison to healthy controls. In control mucosa, IHC staining for occludin and claudin-1 was weak to moderate, cytoplasmic, and membranous, confined to the surface epithelium, while staining in intestinal crypts was negative. On the other hand, an enhanced expression of both proteins in the enteric crypts and surface epithelium was demonstrated in CD patients upon initial examination. Treatment with TNF inhibitors resulted in a significant reduction of claudin-1 expression (p = 0.018) as well as a notable decline of occludin expression (p = 0.08). Occludin and claudin-1 immunostaining was restricted to the surface epithelium in post-treatment biopsies. In addition, the activity of the disease, as estimated by the Crohn’s Disease Activity Index (r = 0.476; p = 0.014) and C-reactive protein (r = 0.411; p = 0.039), was positively correlated with the expression of claudin-1 in the mucosa. Conclusion Active CD is plagued with a disruption of the expression and distribution of claudin-1 and occludin throughout the affected intestinal mucosa. Successful treatment with biological agents induces the restoration of intestinal barrier function, which is associated with an improvement in the patients' clinical condition.