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PWE-079 Longitudinal Assessment of Epithelial and Immune Cell Changes Following Ileostomy Closure in Patients with Ulcerative Colitis
  1. J Landy1,2,
  2. H O Al-Hassi2,
  3. E R Mann2,
  4. S T Peake3,
  5. P J Ciclitira4,
  6. J Nicholls5,
  7. S K Clark6,
  8. S C Knight2,
  9. A L Hart1
  1. 1St Mark’s IBD Unit, St Mark’s Hospital
  2. 2APRG, Imperial College
  3. 3IBD Unit, St Mark’s Hospital
  4. 4Gastroenterology, St Thomas’ Hospital
  5. 5Biosurgery and Surgical Technology, Imperial college
  6. 6Colorectal Surgery, St Mark’s Hospital, London, UK

Abstract

Introduction The interactions between microbiota, epithelial barrier and innate immune responses are important in the pathogenesis of IBD. The ileo-anal pouch offers a unique opportunity to study these inter-relationships before the onset of disease. There are few data regarding tight junction expression or dendritic cell (DC) characteristics following restorative proctocolectomy (RPC). We aimed to assess the relationship between changes in epithelial tight junction expression, dendritic cell phenotype and mucosal cytokine production over the first year following RPC for ulcerative colitis (UC).

Methods Mucosal biopsy samples were taken from the same UC patients undergoing RPC, from the ileostomy afferent loop, the pouch pre-ileostomy closure (P0) and the pouch 6 and 12 months post-ileostomy closure (n = 5). Eptihelial cells expression of zona occludens (ZO)-1, claudin 1 and claudin 2 and DC expression of TLR 2 and 4, CCR9, β7 and CD40 were measured by multicolour flow cytometry. Cytokines were assessed by multiplex ELISA of biopsy supernatants. The paired t-test was used for statistical analysis.

Results Epithelial expression of claudin 2 was increased (p = 0.04) at 6 months and remained elevated at 12 months. No changes were seen in ZO-1 or claudin 1 expression. There was a significant increase in β7 expression on lamina propria DC (p = 0.02), but no differences in DC TLR or CD40 expresssion were seen at 6 months. DC expression of β7 was further elevated (p = 0.005) as well as significantly increased TLR 4 and CD40 expression (p = 0.04). No cytokines were found to be elevated at 6 months, but at 12 months there was a trend towards increased IL6 (p = 0.05).

Conclusion In patients with UC, altered tight junction expression with increased epithelial expression of the “pore-forming” tight junction claudin 2 was an early event after ileostomy closure that preceded the onset of mucosal inflammation. In parallel, more lamina propria DC expressed gut homing markers possibly in response to increased exposure to the changing microbial signals and a more permeable epithelial barrier. These changes in parallel may lead to increased microbial stimulation of DC with increased TLR and co-stimulatory molecule expression that could predispose to the development of inflammation.

Disclosure of Interest J. Landy Grant/Research Support from: The Broad Foundation, H. Al-Hassi: None Declared, E. Mann: None Declared, S. Peake: None Declared, P. Ciclitira: None Declared, J. Nicholls: None Declared, S. Clark: None Declared, S. Knight: None Declared, A. Hart: None Declared

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