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ABSTRACT: Background and aims
Inflammatory bowel disease [IBD] is a chronic relapsing disorder of the gastrointestinal tract, which generally manifests as Crohn's disease [CD] or ulcerative colitis [UC]. These subtypes are heterogeneous in terms of disease location and histological features, while sharing common clinical presentation, genetic associations and, thus, common immune regulatory pathways.Methods
Using miRNA and mRNA coupled transcriptome profiling and systems biology approaches, we report a comprehensive analysis of blood transcriptomes from treatment-naïve [n = 110] and treatment-exposed [n = 177] IBD patients as well as symptomatic [n = 65] and healthy controls [n = 95].Results
Broadly, the peripheral blood transcriptomes of CD and UC patients were similar. However, there was an extensive gene deregulation in the blood of IBD patients, while only a slight deregulation in symptomatic controls, when compared with healthy controls. The deregulated mRNAs and miRNAs are mainly involved in the innate immunity and are especially enriched in neutrophil activation-related pathways. Oxidative phosphorylation and neutrophil activation-related modules were found to be differentially co-expressed among treatment-naïve IBD as compared to healthy controls. In the deregulated neutrophil activation-related co-expression module, IL1B was identified as the central gene. Levels of co-expression among IL1B and chemosensing receptor [CXCR1/2 and FPR1/2] genes were reduced in the blood of IBD patients when compared with healthy controls.Conclusions
Immune dysregulation seen in peripheral blood transcriptomes of treatment-naïve IBD patients is mainly driven by neutrophil activation.
SUBMITTER: Juzenas S
PROVIDER: S-EPMC9351981 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Juzenas Simonas S Hübenthal Matthias M Lindqvist Carl Mårten CM Kruse Robert R Steiert Tim Alexander TA Degenhardt Frauke F Schulte Dominik D Nikolaus Susanna S Zeissig Sebastian S Bergemalm Daniel D Almer Sven S Hjortswang Henrik H Bresso Francesca F Strüning Nina N Kupcinskas Juozas J Keller Andreas A Lieb Wolfgang W Rosenstiel Philip P Schreiber Stefan S D'Amato Mauro M Halfvarson Jonas J Hemmrich-Stanisak Georg G Franke Andre A
Journal of Crohn's & colitis 20220801 7
<h4>Background and aims</h4>Inflammatory bowel disease [IBD] is a chronic relapsing disorder of the gastrointestinal tract, which generally manifests as Crohn's disease [CD] or ulcerative colitis [UC]. These subtypes are heterogeneous in terms of disease location and histological features, while sharing common clinical presentation, genetic associations and, thus, common immune regulatory pathways.<h4>Methods</h4>Using miRNA and mRNA coupled transcriptome profiling and systems biology approaches ...[more]