Detailed Transcriptional Landscape of Peripheral Blood Points to Increased Neutrophil Activation in Treatment-Naïve Inflammatory Bowel Disease

Detailed Transcriptional Landscape of Peripheral Blood Points to Increased Neutrophil Activation in Treatment-Naïve Inflammatory Bowel Disease. Juzenas, S., Hübenthal, M., Lindqvist, C. M., Kruse, R., Steiert, T. A., Degenhardt, F., Schulte, D., Nikolaus, S., Zeissig, S., Bergemalm, D., Almer, S., Hjortswang, H., Bresso, F., Group, S. I. W., Strüning, N., Kupcinskas, J., Keller, A., Lieb, W., Rosenstiel, P., Schreiber, S., D’Amato, M., Halfvarson, J., Hemmrich-Stanisak, G., & Franke, A. Journal of Crohn's and Colitis, 01, 2022. jjac003

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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.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].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.Immune dysregulation seen in peripheral blood transcriptomes of treatment-naïve IBD patients is mainly driven by neutrophil activation.

@article{10.1093/ecco-jcc/jjac003,
    author = {Juzenas, Simonas and Hübenthal, Matthias and Lindqvist, Carl Mårten and Kruse, Robert and Steiert, Tim Alexander and Degenhardt, Frauke and Schulte, Dominik and Nikolaus, Susanna and Zeissig, Sebastian and Bergemalm, Daniel and Almer, Sven and Hjortswang, Henrik and Bresso, Francesca and SIC IBD Working Group and Strüning, Nina and Kupcinskas, Juozas and Keller, Andreas and Lieb, Wolfgang and Rosenstiel, Philip and Schreiber, Stefan and D’Amato, Mauro and Halfvarson, Jonas and Hemmrich-Stanisak, Georg and Franke, Andre},
    title = "{Detailed Transcriptional Landscape of Peripheral Blood Points to Increased Neutrophil Activation in Treatment-Naïve Inflammatory Bowel Disease}",
    journal = {Journal of Crohn's and Colitis},
    year = {2022},
    month = {01},
    abstract = "{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.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].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.Immune dysregulation seen in peripheral blood transcriptomes of treatment-naïve IBD patients is mainly driven by neutrophil activation.}",
    issn = {1873-9946},
    doi = {10.1093/ecco-jcc/jjac003},
    url = {https://doi.org/10.1093/ecco-jcc/jjac003},
    note = {jjac003},
    eprint = {https://academic.oup.com/ecco-jcc/advance-article-pdf/doi/10.1093/ecco-jcc/jjac003/42601153/jjac003.pdf},
}

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