Detailed transcriptional landscape of peripheral blood points to increased neutrophil activation in treatment-naïve inflammatory bowel diseaseInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
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.
Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
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.
Department of Medicine, Karolinska Institutet, Solna, and Division of Gastroenterology, Karolinska University Hospital, Stockholm, Sweden.
Department of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden; Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden.
Department of Medicine, Karolinska Institutet, Solna, and Division of Gastroenterology, Karolinska University Hospital, Stockholm, Sweden.
Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany. (SIC IBD working group)
Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Institute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; University Hospital of Schleswig-Holstein (UKSH), Kiel Campus, Kiel, Germany .
Visa övriga samt affilieringar
2022 (Engelska)Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 16, nr 7, s. 1097-1109Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
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.
Ort, förlag, år, upplaga, sidor
Oxford University Press, 2022. Vol. 16, nr 7, s. 1097-1109
Nyckelord [en]
Inflammatory bowel disease, gene expression, peripheral blood
Nationell ämneskategori
Gastroenterologi och hepatologi
Identifikatorer
URN: urn:nbn:se:oru:diva-96450DOI: 10.1093/ecco-jcc/jjac003ISI: 000760458900001PubMedID: 35022690Scopus ID: 2-s2.0-85132374171OAI: oai:DiVA.org:oru-96450DiVA, id: diva2:1627671
Forskningsfinansiär
Europeiska kommissionen, 733100Stiftelsen för strategisk forskning (SSF), RB13-0160Vetenskapsrådet, 2020-02021
Anmärkning
Funding agency:
German Research Foundation (DFG) EXC 2167
2022-01-142022-01-142025-02-11Bibliografiskt granskad