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Predictive value of epithelial gene expression profiles for response to infliximab in Crohn's disease‡

Arijs, Ingrid MS1,2; Quintens, Roel MS2; Van Lommel, Leentje MS2; Van Steen, Kristel PhD3; De Hertogh, Gert MD, PhD4; Lemaire, Katleen PhD2; Schraenen, Anica MS2; Perrier, Clémentine PhD1; Van Assche, Gert MD, PhD1; Vermeire, Séverine MD, PhD1; Geboes, Karel MD, PhD4; Schuit, Frans MD, PhD2,*; Rutgeerts, Paul MD, PhD, FRCP1,5,†

doi: 10.1002/ibd.21301
Original Clinical Articles: IFX Predictive Response Signature in CD: Original Article

Background: Infliximab (IFX) has become the mainstay of therapy of refractory Crohn's disease (CD). However, a subset of patients shows incomplete or no response to this agent. In this study we investigated whether we could identify a mucosal gene panel to predict (non)response to IFX in CD.

Methods: Mucosal biopsies were obtained during endoscopy from 37 patients with active CD (19 Crohn's colitis [CDc] and 18 Crohn's ileitis [CDi]) before and after first IFX treatment. Response was defined based on endoscopic and histologic findings. Total RNA was analyzed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to confirm microarray data.

Results: At baseline, significant gene expression differences were found between CDc and CDi. For predicting response in CDc, comparative analysis of CDc pretreatment expression profiles identified 697 significant probe sets between CDc responders (n = 12) and CDc nonresponders (n = 7). Class prediction analysis of CDc top 20 and top 5 significant genes allowed complete separation between CDc responders and CDc nonresponders. The CDc top 5 genes were TNFAIP6, S100A8, IL11, G0S2, and S100A9. Only one patient with CDi completely healed the ileal mucosa. Even using less stringent response criteria, we could not identify a predictive gene panel for IFX responsiveness in CDi.

Conclusions: This study identified a 100% accurate predictive gene signature for (non)response to IFX in CDc, whereas no such a predictive gene set could be identified for CDi. Inflamm Bowel Dis 2010

1Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium

2Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, Leuven, Belgium

3Department of Electrical Engineering and Computer Science (Montefiore Institute), University of Liège, Liège, Belgium

4Department of Morphology and Molecular Pathology, University Hospital Gasthuisberg, Leuven, Belgium

5Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, Leuven, Belgium

*Reprints: Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, Herestraat 49, mailbox 901, B-3000 Leuven, Belgium

Department of Gastroenterology, University of Hospital Gasthuisberg, Herestraat 49, mailbox 7003, B-3000 Leuven, Belgium

Email: Frans.Schuit@med.kuleuven.be

Email: paul.rutgeerts@uz.kuleuven.be

Received for publication 16 February 2010; Accepted 24 February 2010.

Published online 6 April 2010 in Wiley Online Library (wileyonlinelibrary.com).

Supported by a grant from the Fund for Scientific Research – Flanders (FWO) Belgium (FWO project nr.G.0440.06). P.R., S.V., G.V.A., and K.G. report the following conflicts of interest: grant support, lecture fees and consulting fees from Centocor and Schering-Plough.

Additional supporting information may be found in the online version of this article.

© Crohn's & Colitis Foundation of America, Inc.
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