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* = Presenting author

P681. Serum and tissue micro-RNA expression profiles in different stages of inflammatory bowel disease

M. Iborra1, F. Bernuzzi2, B. Beltrán1, M. Locati3, P. Nos4, P. Invernizzi5, S. Danese6, 1Hospital La Fe, Gastroenterology. CIBEREHD, Valencia, Spain, 2IRCCS Istituto Clinico Humanitas, Division of Internal Medicine and Hepatobiliary Immunopathology, Milano, Italy, 3IRCCS Istituto Clinico Humanitas, Laboratorio di Biologia dei Leucociti, Milano, Italy, 4Hospital La Fe, Gastroenterology. CIBERehd, Valencia, Spain, 5IRCCS Istituto Clinico Humanitas, Division of Rheumatology, Allergy and Clinical, Milano, Italy, 6IRCCS Istituto Clinico Humanitas, Division of Gastroenterology, Milano, Italy

Background

Inflammatory Bowel Disease (IBD) is associated with the differential expression of genes involved in inflammation and immune functions. MicroRNAs (miRNAs) are involved in the regulation of biological processes, as well as in the induction of chronic inflammatory diseases and autoimmune diseases.

Aims: (1) To establish specific miRNAs expression patterns in serum and mucosa of Crohn's disease (CD) and ulcerative colitis (UC) patients at different stages of the disease and to compare with healthy subjects (HS). (2) To correlate serum and tissue miRNA expression patterns. (3) To identify miRNA targets.

Methods

Samples of serum and biopsies were obtained from 9 active CD (aCD), 9 inactive CD (iCD), 9 active UC (aUC) and 9 inactive UC (iUC). Serum from 33 HS was collected. Three pools of three samples were analyzed for each group. The miRNA was isolated by the mirVanaTMPARISTM kit (Applied Biosystems). The small RNA fraction was reverse transcribed using the miRNA Megaplex RT primers and TaqMan® microRNA Reverse Transcription kit (Applied Biosystems). Up to 700 miRNAs were evaluated by TaqManR Human miRNA Array. The delta-Ct values were obtained using the mean expression value of all expressed miRNAs in a given sample as a normalization factor for miRNA real-time quantitative PCR data. P < 0.05 was considered significant.

Results

Nineteen miRNAs were significantly increased and 2 miRNAs were significantly decreased in serum of CD patients as compared to HS. Six serum miRNAs were exclusively regulated in aCD as compared to iCD patients. Thirty-seven miRNAs were significantly increased and 2 miRNAs were significantly decreased in serum of UC patients as compared to HS. None serum miRNA was exclusively regulated in aUC when compared with iUC. There were 14 serum miRNAs commonly expressed in CD and UC patients. Four miRNAs were increased and 3 were decreased in mucosa of aCD as compared to iCD. None serum miRNAs coincided with tissue miRNAs in aCD patients. Two miRNAs were increased and 3 were decreased in mucosa of aUC as compared to iUC. None serum miRNAs coincided with tissue miRNAs in aUC patients. Some discovered miRNAs are implicated in important inflammatory pathways.

Conclusion

Specific miRNA expression patterns may be associated to IBD and to their different stages (active and inactive disease). MiRNAs could be useful to distinguish IBD from HS and support their utility as possible biomarkers. Further studies based on miRNA are required as therapeutic targets.