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PTU-105 Expression Of Micrornas Mir-31, Mir-146a And Mir-155 Is Significantly Elevated In Anti-tnf-alpha Treatment Failure In Colonic Cd
  1. M Gwiggner1,
  2. RT Martinez-Nunez1,
  3. T Sanchez-Elsner1,
  4. J Cummings2
  1. 1Clinical and Experimental Sciences, University or Southampton, Southampton General Hospital, UK
  2. 2Department of Gastroenterology, University Hospital Southampton NHS Trust, Southampton, UK

Abstract

Introduction Crohn’s disease (CD) is a Th1/Th17 driven disease in which TNF-α and INF-γ play important roles. Anti-TNF-α drugs are used in moderate-severe CD to induce and maintain remission. Mucosal healing is an aim of therapy. MicroRNAs are non‐coding RNAs which control translation of mRNA. MiR-31, miR-146a and miR-155 are involved in the regulation of immune responses and are deregulated in CD. Aim of this study is to evaluate the impact of medical treatment on microRNA expression in CD and to investigate microRNAs as biomarkers in CD.

Methods 37 patients with colonic CD undergoing colonoscopy were recruited. A partial Simple Endoscopic Score for CD (SES-CD) was assessed. Sigmoid biopsies were taken from 19 patients in remission (SES-CD=0) and 18 patients with active sigmoid CD (SES-CD1). Remission (R) was defined as mucosal healing (SES-CD=0) and treatment failure (F) as an SES-CD1 in the left colon. MicroRNA (miR-31, miR-146a and miR-155) and mRNA expression (TNF- α, INF-γ) were evaluated by qPCR. Sub-analysis compared treatment naïve patients (6 inactive/8 active) to patients on thiopurines (TP) (R= 5/F= 5) and anti-TNF-α therapy (R=6/F=7).

Results miR-31, miR-146a and miR-155 were significantly up-regulated as were TNF-α and INF-γ in active sigmoid CD compared to patients in remission. Patients on TP compared to treatment naïve patients showed significant down-regulation of TNF-α and INF-γ in remission, compared to treatment naïve patients with active CD. MicroRNA levels in TP failure were interstingly lower compared to patients in remission. In contrast, microRNA levels in the anti-TNF-α group in therapy failure were significantly elevated compared to active treatment naïve patients, behaving opposite to patients on TP. MicroRNA expression in remission showed levels similar to treatment naïve patients in remission. While TNF-α and INF-γ returned to base levels in remission on anti-TNF-α drugs, significantly lower compared to active treatment naïve CD, in therapy failure TNF-α remained elevated and INF-γ was significantly raised.

Conclusion Our data reveals a clear up-regulation of miR-31, miR-146 and miR-155 as well as of TNF- α and INF-γ in active colonic CD. TP and anti-TNF-α drugs significantly alter the expression of microRNAs miR-31, miR-146a and miR-155 compared to treatment naïve patients behaving in an opposing manner. MicroRNAs remain significantly elevated in patients with sigmoid CD failing to respond to anti-TNF-α treatment. MicroRNAs expression profiles may have a role as biomarkers in predicting treatment failure in CD.

Disclosure of Interest None Declared.

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