| 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 com
pared 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 com
pared with healthy controls.
Conclusions: Immune dysregulation seen in peripheral blood transcriptomes of treatment-naïve IBD patients is mainly driven by neutrophil
activation. |
