Detailed transcriptional landscape of peripheral blood points to increased neutrophil activation in treatment-naïve inflammatory bowel disease

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Detailed transcriptional landscape of peripheral blood points to increased neutrophil activation in treatment-naïve inflammatory bowel disease

Juzenas, Simonas (författare): Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Institute of Biotechnology, Life Science Centre, Vilnius University, Vilnius, Lithuania,Christian Albrechts Univ Kiel, Germany; Vilnius Univ, Lithuania

Hübenthal, Matthias (författare): Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Department of Dermatology, Quincke Research Center, University Hospital Schleswig-Holstein, Kiel, Germany,Christian Albrechts Univ Kiel, Germany; Univ Hosp Schleswig Holstein, Germany

Lindqvist, Carl Mårten, 1979- (författare): Örebro universitet,Institutionen för medicinska vetenskaper,Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany,Christian Albrechts Univ Kiel, Germany; Orebro Univ, Sweden

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Kruse, Robert, 1972- (författare): Örebro universitet,Institutionen för medicinska vetenskaper,Department of Clinical Research Laboratory,iRiSC - Inflammatory Response and Infection Susceptibility Centre,Orebro Univ, Sweden; Orebro Univ, Sweden

Steiert, Tim Alexander (författare): Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany,Christian Albrechts Univ Kiel, Germany

Degenhardt, Frauke (författare): Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany,Christian Albrechts Univ Kiel, Germany

Schulte, Dominik (författare): Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine I, University Hospital of Schleswig-Holstein, Kiel, Germany; Institute of Diabetes and Clinical Metabolic Research, Kiel University, Kiel, Germany,Univ Hosp Schleswig Holstein, Germany; Univ Kiel, Germany

Nikolaus, Susanna (författare): Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany,Univ Hosp Schleswig Holstein, Germany

Zeissig, Sebastian (författare): Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany,Tech Univ Dresden TU Dresden, Germany; Tech Univ TU Dresden, Germany

Bergemalm, Daniel, 1977- (författare): Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Orebro Univ, Sweden

Almer, Sven (författare): Department of Medicine, Karolinska Institutet, Solna, and Division of Gastroenterology, Karolinska University Hospital, Stockholm, Sweden,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden

Hjortswang, Henrik (författare): Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken

Bresso, Francesca (författare): Karolinska Institutet

Strüning, Nina (författare): Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany,SIC IBD working group,Univ Hosp Schleswig Holstein, Germany

Kupcinskas, Juozas (författare): Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania,Lithuanian Univ Hlth Sci, Lithuania; Lithuanian Univ Hlth Sci, Lithuania

Keller, Andreas (författare): Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA,Saarland Univ, Germany; Stanford Univ, CA 94305 USA

Lieb, Wolfgang (författare): Institute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany,Christian Albrechts Univ Kiel, Germany

Rosenstiel, Philip (författare): Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany,Christian Albrechts Univ Kiel, Germany

Schreiber, Stefan (författare): Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany,Christian Albrechts Univ Kiel, Germany; Univ Hosp Schleswig Holstein, Germany

D'Amato, Mauro (författare): Karolinska Institutet

Halfvarson, Jonas, 1970- (författare): Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology,Orebro Univ, Sweden

Hemmrich-Stanisak, Georg (författare): Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany,Christian Albrechts Univ Kiel, Germany

Franke, Andre (författare): Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; University Hospital of Schleswig-Holstein (UKSH), Kiel Campus, Kiel, Germany,Christian Albrechts Univ Kiel, Germany; Univ Hosp Schleswig Holstein UKSH, Germany

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2022-01-11
2022
Engelska.
Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 16:7, s. 1097-1109

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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, the IL1B was identified as the central gene. The co-expression levels 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.

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Detailed transcriptional landscape of peripheral blood points to increased neutrophil activation in treatment-naïve inflammatory bowel disease

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