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P102. Altered epithelial tight junction expression and elevated IL 6 levels in pouchitis

J. Landy1, H. Omar Al-Hassi2, E. Ronde2, E. Mann2, S. Peake1, R. Man3, P.J. Ciclitira4, R.J. Nicholls5, S.K. Clark6, S. Knight2, A.L. Hart1, 1St Mark's Hospital, IBD Unit, London, United Kingdom, 2Antigen Presentation Research Group, Imperial College, London, United Kingdom, 3St Mark's Hospital, Endoscopy Department, London, United Kingdom, 4St Thomas' Hospital, Gastroenterology, London, United Kingdom, 5Imperial College, Department of Biosurgery and Surgical Technology, London, United Kingdom, 6St Mark's Hospital, Colorectal Surgery, London, United Kingdom

Background

Intestinal epithelial barrier function limits the interactions between microbial antigens and the mucosal immune system. In IBD, epithelial barrier function is impaired with altered expression of tight junctions. We aimed to assess epithelial tight junction expression and mucosal cytokines in acute and chronic pouchitis and non-inflamed pouches of patients with ulcerative colitis.

Methods

Mucosal biospy samples were taken from ulcerative colitis patients with pouchitis (chronic pouchitis n = 9, acute pouchitis n = 4) and those without pouchitis (n = 11). Epithelial cells were isolated from biopsy tissue after incubation with DTT and EDTA. Eptihelial cell expression of ZO-1, claudin 1 and claudin 2 were measured by multicolour flow cytometry. Cytokines were assessed by multiplex ELISA of biopsy supernatants. The t-test was used for statistical analysis.

Results

In acute pouchitis ZO-1 was elevated compared with both chronic pouchitis and non-pouchitis (p = 0.008), whilst in chronic pouchtis ZO-1 expression was reduced compared with non pouchitis (p = 0.006). Claudin 1 expression was reduced in chronic pouchitis (p = 0.04), but was not significantly reduced in acute pouchitis. In acute pouchitis, claudin 2 expression was elevated (p ≤ 0.001), but was not increased in chronic pouchitis. IL6 levels were elevated in chronic pouchitis compared with non pouchitis patients (p = 0.01).

Conclusion

Epithelial tight junction expression was altered in pouchitis in association with increased IL6 levels. Increased claudin 2 expression in acute, but not chronic pouchitis may represent early pathological changes in the development of pouch inflammation. In chronic inflammation the tight junction complex was deranged with reduced expression of both claudin 1 and ZO-1. Increased epithelial barrier permeability due to altered tight junction expression may be a critical mechanism in the development and perpetuation of pouch inflammation.