title: Predictive value of epithelial gene expression profiles for response to infliximab in Crohn's disease.
abstract: 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.
authors.affiliation: Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Arijs
authors.forename: Roel
authors.initials: R
authors.lastname: Quintens
authors.forename: Leentje
authors.initials: L
authors.lastname: Van Lommel
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Steen
authors.forename: Gert
authors.initials: G
authors.lastname: De Hertogh
authors.forename: Katleen
authors.initials: K
authors.lastname: Lemaire
authors.forename: Anica
authors.initials: A
authors.lastname: Schraenen
authors.forename: Clémentine
authors.initials: C
authors.lastname: Perrier
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D006801:Humans; D007079:Ileitis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016879:Salvage Therapy
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D005765:Gastrointestinal Agents; D012333:RNA, Messenger; D000069285:Infliximab