Predictive value of epithelial gene expression profiles for response to infliximab in Crohn's disease.
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.
Arijs
Ingrid
I
Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
Quintens
Roel
R
Van Lommel
Leentje
L
Van Steen
Kristel
K
De Hertogh
Gert
G
Lemaire
Katleen
K
Schraenen
Anica
A
Perrier
Clémentine
C
Van Assche
Gert
G
Vermeire
Séverine
S
Geboes
Karel
K
Schuit
Frans
F
Rutgeerts
Paul
P
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
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D005765:Gastrointestinal Agents; D012333:RNA, Messenger; D000069285:Infliximab