Whole Genome Gene Expression Meta-Analysis of Inflammatory Bowel Disease Colon Mucosa Demonstrates Lack of Major Differences between Crohn's Disease and Ulcerative Colitis

Abstract

BackgroundIn inflammatory bowel disease (IBD), genetic susceptibility together with environmental factors disturbs gut homeostasis producing chronic inflammation. The two main IBD subtypes are Ulcerative colitis (UC) and Crohn’s disease (CD). We present the to-date largest microarray gene expression study on IBD encompassing both inflamed and un-inflamed colonic tissue. A meta-analysis including all available, comparable data was used to explore important aspects of IBD inflammation, thereby validating consistent gene expression patterns.MethodsColon pinch biopsies from IBD patients were analysed using Illumina whole genome gene expression technology. Differential expression (DE) was identified using LIMMA linear model in the R statistical computing environment. Results were enriched for gene ontology (GO) categories. Sets of genes encoding antimicrobial proteins (AMP) and proteins involved in T helper (Th) cell differentiation were used in the interpretation of the results. All available data sets were analysed using the same methods, and results were compared on a global and focused level as t-scores.ResultsGene expression in inflamed mucosa from UC and CD are remarkably similar. The meta-analysis confirmed this. The patterns of AMP and Th cell-related gene expression were also very similar, except for IL23A which was consistently higher expressed in UC than in CD. Un-inflamed tissue from patients demonstrated minimal differences from healthy controls.ConclusionsThere is no difference in the Th subgroup involvement between UC and CD. Th1/Th17 related expression, with little Th2 differentiation, dominated both diseases. The different IL23A expression between UC and CD suggests an IBD subtype specific role. AMPs, previously little studied, are strongly overexpressed in IBD. The presented meta-analysis provides a sound background for further research on IBD pathobiology.

P015. Exploring the barrier; RNA sequencing of laser microdissected epithelium from IBD patients

“…Results: The analysis resulted in > 4000 differentially expressed (DE) genes between UC and N samples. The resulting list of DE genes agreed with previously published Results from analysis of full thickness pinch biopsies [1]. Genes previously identified as highly expressed in the epithelium of UC colon are also found to be DE between the LCM samples [2].…”

“…By isolating the gene expression to the epithelial monolayer (EM), we identify epithelial processes important in IBD pathophysiology without needing to take contribution from infiltrating inflammatory cells into consideration. Methods: Pinch biopsies from colonic mucosa of six UC patients and N subjects were collected as previously described [1]. An area corresponding to approx.…”

Mucosal Toll-like Receptor 3-dependent Synthesis of Complement Factor B and Systemic Complement Activation in Inflammatory Bowel Disease

“…In the microarray gene expression study on colonic biopsies from IBD patients and healthy controls done previously 6,19 , we now show a significant upregulation of CFB in both active UC and CD vs. non-diseased mucosa and also vs. healthy controls (Fig.3). In active UC …”

The Role of T-Cell Subsets in Chronic Inflammation in Celiac Disease and Inflammatory Bowel Disease Patients: More Common Mechanisms or More Differences?

“…IL-17 is expressed in the inflamed mucosa of UC patients [83,106,133,134]. Like in CD, IL-23 from CD14 + CD68 + macrophages promote Th17-cell immune responses crucially contributing to the chronic local inflammation of UC [135,136].…”