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P062. Ileal gene expression profiling of Crohn's disease underlines the importance of the inflammatory load during the disease course

J. Van der Goten1, I. Arijs1, L. Van Lommel2, K. Machiels1, G. De Hertogh1, M. Ferrante1, F. Schuit2, S. Vermeire1, P. Rutgeerts1, 1KU Leuven, Translational Research in GastroIntestinal Disorders (TARGID), Leuven, Belgium, 2KU Leuven, Gene Expression Unit, Department of Molecular Cell Biology, Leuven, Belgium


Crohn's disease (CD) is characterized by intestinal inflammation progressing to stricturing and/or penetrating complications in most patients. Biologic treatment seems more effective in the early phase of CD. This study compared ileal gene expression profiles of patients with newly diagnosed CD, post-operative recurrent (POR) CD or late CD and controls to see if gene expression differences could explain the changing disease behavior over time.


Ileal inflamed mucosal biopsies were obtained from 15 patients with <2 year diagnosis (=early CD), 19 patients with POR CD (Rutgeerts' score i3-i4) <1 year after ileo-colonic resection, 14 patients >2 years after diagnosis or ileo-colonic resection (= late CD) and 12 controls. Total RNA from biopsies was used to analyze gene expression via Affymetrix Human Gene 1.0 ST arrays. Data was analyzed with Bioconductor software.


With comparative analyses, only small gene expression differences were identified between the different CD groups, while many differences were observed with controls. In early vs. late CD, we identified only 1 significantly different (false discovery rate <5% and >2-fold change) gene probe set (NPC1L1). In POR vs. late CD, the expression of 4 gene probe sets (MUC5B, S100P, C12orf75, C12orf36) was significantly decreased. In early vs. POR CD, we identified 28 significantly different gene probe sets, incl. 2 CD susceptibility genes (FAIM3 ↑, ABCG5 ↓), 1 antimicrobial peptide (C5 ↓) and 1 cell-adhesion molecule (CCL19 ↑). As compared to controls, we identified in early, POR and late CD respectively 580, 355 and 601 significantly different gene probe sets mainly involved in inflammatory pathways, with a great overlap between these comparisons. Next, we included IL8 expression as a confounder to exclude the effect of the inflammatory load. After comparison with controls, only a small amount remained significantly different: 23 gene probe sets in early CD (incl. ITLN1, LCN2, MUC1, MUC4), 96 in POR CD (incl. ITLN1, MUC1, LCN2, CLDN18, CDHR1, LIN7A, C5, NOS2, CCL28) and 13 in late CD. This indicates that the majority of significant gene probe sets in comparisons with controls are related to the inflammatory load.


There are no different pathogenic mechanisms for early and late disease, highlighting the relativity of time in the natural evolution of CD. We underline the importance of the severity of the inflammatory process during the disease course and the necessity to early interrupt the inflammatory cascade.