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

Ingrid Arijs; Roel Quintens; Leentje Van Lommel; Kristel Van Steen; Gert De Hertogh; Katleen Lemaire; Anica Schraenen; Clémentine Perrier; Gert Van Assche; Séverine Vermeire; Karel Geboes; Frans Schuit; Paul Rutgeerts; Sarah Baatout

doi:10.1002/ibd.21301

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

Ingrid Arijs, Roel Quintens, Leentje Van Lommel, Kristel Van Steen, Gert De Hertogh, Katleen Lemaire, Anica Schraenen, Clémentine Perrier, Gert Van Assche, Séverine Vermeire, Karel Geboes, Frans Schuit, Paul Rutgeerts, Sarah Baatout

Research output › peer-review

Abstract

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 response to IFX in CD. 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 U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. 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 and CDc nonresponders. 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. This study identified a 100% accurate predictive gene signature for response to IFX in CDc, whereas no predictive gene set could be identified for CDi.

Original language	English
Pages (from-to)	2090-2098
Journal	Inflammatory Bowel Diseases
Volume	16
Issue number	12
DOIs	https://doi.org/10.1002/ibd.21301
State	Published - Dec 2010

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Arijs, I., Quintens, R., Van Lommel, L., Van Steen, K., De Hertogh, G., Lemaire, K., Schraenen, A., Perrier, C., Van Assche, G., Vermeire, S., Geboes, K., Schuit, F., Rutgeerts, P., & Baatout, S. (2010). Predictive value of epithelial gene expression profiles for response to infliximab in Crohn's disease. Inflammatory Bowel Diseases, 16(12), 2090-2098. https://doi.org/10.1002/ibd.21301

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title = "Predictive value of epithelial gene expression profiles for response to infliximab in Crohn's disease",

abstract = "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 response to IFX in CD. 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 U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. 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 and CDc nonresponders. 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. This study identified a 100% accurate predictive gene signature for response to IFX in CDc, whereas no predictive gene set could be identified for CDi.",

keywords = "Crohn's disease, infliximab, mucosal gene expression profiling",

author = "Ingrid Arijs and Roel Quintens and {Van Lommel}, Leentje and {Van Steen}, Kristel and {De Hertogh}, Gert and Katleen Lemaire and Anica Schraenen and Cl{\'e}mentine Perrier and {Van Assche}, Gert and S{\'e}verine Vermeire and Karel Geboes and Frans Schuit and Paul Rutgeerts and Sarah Baatout",

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Arijs, I, Quintens, R, Van Lommel, L, Van Steen, K, De Hertogh, G, Lemaire, K, Schraenen, A, Perrier, C, Van Assche, G, Vermeire, S, Geboes, K, Schuit, F, Rutgeerts, P & Baatout, S 2010, 'Predictive value of epithelial gene expression profiles for response to infliximab in Crohn's disease', Inflammatory Bowel Diseases, vol. 16, no. 12, pp. 2090-2098. https://doi.org/10.1002/ibd.21301

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AU - De Hertogh, Gert

AU - Lemaire, Katleen

AU - Schraenen, Anica

AU - Perrier, Clémentine

AU - Van Assche, Gert

AU - Vermeire, Séverine

AU - Geboes, Karel

AU - Schuit, Frans

AU - Rutgeerts, Paul

A2 - Baatout, Sarah

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N2 - 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 response to IFX in CD. 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 U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. 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 and CDc nonresponders. 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. This study identified a 100% accurate predictive gene signature for response to IFX in CDc, whereas no predictive gene set could be identified for CDi.

AB - 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 response to IFX in CD. 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 U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. 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 and CDc nonresponders. 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. This study identified a 100% accurate predictive gene signature for response to IFX in CDc, whereas no predictive gene set could be identified for CDi.

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KW - infliximab

KW - mucosal gene expression profiling

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SN - 1078-0998

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