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P040. Mucosal T cell profiles in newly diagnosed, untreated inflammatory bowel disease patients

C. Horjus1, M.J. Groenen2, P.J. Wahab3, E. van Lochem4, 1Radboud University, Gastroenterology and hepatology, Nijmegen, Netherlands, 2Rijnstate Hospital, Gastroenterology and hepatology, Arnhem, Netherlands, 3Rijnstate Hospital, Gastroenterology and hepatology, Nijmegen, Netherlands, 4Rijnstate Hospital, Medical Microbiology and Immunology, Arnhem, Netherlands

Background

Inflammatory bowel disease (IBD) represents a heterogeneous group of disorders associated with imbalances in the intestinal adaptive immune response. In an attempt to explain its diversity in clinical presentation and disease course, we set out to investigate the phenotype of the T cell subpopulations and the related cytokine network in the gastrointestinal mucosa of naïve, untreated IBD patients.

Methods

Mucosal biopsies from duodenum, ileum and colon mucosa of newly diagnosed, untreated patients with Crohn's disease (CD, n = 51), Ulcerative Colitis (UC, n = 14) and controls (n = 14) were obtained. Flow cytometry was used to analyse the expression of maturation and activation markers on gut-infiltrating T cells. The remaining mucosal lymphocytes were stimulated overnight with PMA and ionomycin where after the supernatants were analyzed for proinflammatory cytokines by cytometric bead array. The endoscopic disease activity was scored by using the Simple Endoscopy Score in CD and the endoscopic Mayo score in UC.

Results

Irrespective of the IBD phenotype, the frequency of B cells, CD4+CD103− and FoxP3+/CD25high T cells was much higher in the colon/ileum than in duodenum. We identified four mucosal T cell profiles according to the expression of maturation and activation markers CD45RA+and CD27+: profile A: high percentages (>40%) CD45RA+CD27+ T cells; profile B: high percentages (>40%) CD45RA−CD27+ T cells; profile C: high percentages (>40%) CD45RA−CD27− T cells, and profile D: equal relative numbers of these before mentioned subpopulations. Within the ileum/colon mucosa, profile D was only seen in controls while profile A was only seen in patients, both CD and UC. However, profile A was associated with upper gastrointestinal location and perianal disease in CD. Surprisingly, profile A expressed a significantly higher amount of TNFalfa (30% vs. 17%, p = 0.004 in CD; 32% vs. 19%, p 0.118 in UC) and a lower amount of IFN-gamma (47% vs. 66%, p = 0.003 in CD; 47% vs. 63%, p = 0.340 in UC) than profile C. There was no correlation between these profiles and the endoscopic disease activity.

Conclusion

Our results suggest that there are different mucosal T cell maturation profiles with distinct cytokine responses, in the very early phase of untreated IBD. This could in part explain the heterogeneity of the clinical presentation and response to immunomodulating therapies in IBD.