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P088. Differential expression of prolyl hydroxylases 1 and 3 between IBD and non-IBD patients

S. Van Welden1, D. Laukens1, M. De Vos1, P. Hindryckx1, 1Ghent University Hospital, Gastroenterology, Ghent, Belgium

Background

Prolyl hydroxylase inhibition has been proposed as a promising alternative strategy in the treatment of inflammatory bowel disease (IBD). In this study we explored the colonic mucosal expression of the different prolyl hydroxylase-isoforms (PHD1, 2 and 3) in order to identify the key isoform(s) involved in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC).

Methods

Biopsies were taken in macroscopically inflamed and non-inflamed areas of UC and CD patients. Samples of healthy controls and inflamed regions of patients with infectious colitis were included as controls. Next, the expression of PHD1, 2 and 3 was analysed using qRT-PCR in a medication naïve cohort (N = 79) and results were validated in a second cohort, which also included patients that received immunosuppressive agents (N = 89).

Results

Gene expression analysis revealed a significant increase of PHD1 in inflamed colonic biopsies of both UC (P < 0.0001) and CD patients (P < 0.05) when compared to healthy controls. A same trend was observed in patients with infectious colitis (P = 0.063). Interestingly, only inflamed colonic samples of UC patients showed a significant up-regulation of PHD3 mRNA levels (P < 0.0001) compared to healthy controls. This was not seen in patients with active CD, nor in patients with infectious colitis. All results were confirmed in a second cohort of patients and were not influenced by the use of immunosuppressive agents.

Conclusion

We have identified an altered expression pattern of PHD1 and 3 in patients with IBD. PHD1 appears to be the most appealing target for therapeutic intervention in the treatment of colitis. In addition, increased colonic PHD3 expression may have potential as a new diagnostic marker for UC.