Schäffler H, Rohde M, Rohde S, Huth A, Gittel N, Hollborn H, Koczan D, Glass Ä, Lamprecht G, Jaster R. NOD2- and disease-specific gene expression profiles of peripheral blood mononuclear cells from Crohn’s disease patients. World J Gastroenterol 2018; 24(11): 1196-1205 [PMID: 29568200 DOI: 10.3748/wjg.v24.i11.1196]
Corresponding Author of This Article
Robert Jaster, MD, Academic Research, Professor, Senior Scientist, Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, E.-Heydemann-Str. 6, Rostock 18057, Germany. robert.jaster@med.uni-rostock.de
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Mar 21, 2018; 24(11): 1196-1205 Published online Mar 21, 2018. doi: 10.3748/wjg.v24.i11.1196
NOD2- and disease-specific gene expression profiles of peripheral blood mononuclear cells from Crohn’s disease patients
Holger Schäffler, Maria Rohde, Sarah Rohde, Astrid Huth, Nicole Gittel, Hannes Hollborn, Dirk Koczan, Änne Glass, Georg Lamprecht, Robert Jaster
Holger Schäffler, Maria Rohde, Sarah Rohde, Astrid Huth, Nicole Gittel, Hannes Hollborn, Georg Lamprecht, Robert Jaster, Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock 18057, Germany
Dirk Koczan, Institute of Immunology, Rostock University Medical Center, Rostock 18057, Germany
Änne Glass, Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock 18057, Germany
Author contributions: Schäffler H, Rohde S and Jaster R designed the study; Huth A, Schäffler H and Lamprecht G took responsibility for patient care and follow-up; Rohde M, Rohde S, Hollborn H, Jaster R and Koczan D (microarray studies) performed the experiments; Gittel N, Huth A and Schäffler H collected the samples and performed the clinical characterization of the patients; Glass Ä performed the biostatistics; all authors analyzed the data; and Schäffler H and Jaster R wrote the manuscript.
Supported by a grant from the Damp-Foundation (2016-04) to Schäffler H and Rohde S.
Institutional review board statement: The study was approved by the ethics board of the Medical Faculty of the University of Rostock (A 2015-0042). Written informed consent was obtained from each participant prior to enrollment.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Robert Jaster, MD, Academic Research, Professor, Senior Scientist, Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, E.-Heydemann-Str. 6, Rostock 18057, Germany. robert.jaster@med.uni-rostock.de
Telephone: +49-381-4947349 Fax: +49-381-4947482
Received: December 21, 2017 Peer-review started: December 21, 2017 First decision: January 18, 2018 Revised: January 29, 2018 Accepted: February 1, 2018 Article in press: February 1, 2018 Published online: March 21, 2018 Processing time: 84 Days and 22.4 Hours
ARTICLE HIGHLIGHTS
Research background
In Crohn’s disease (CD), the interplay of genetic and environmental factors converges at the level of an altered antipathogenic immune response, which is incompletely understood. Peripheral blood mononuclear cells (PBMCs) provide a useful tool to study elements of the immunopathogenesis of the disease in vitro.
Research motivation
Currently, there is a lack of biomarkers to predict the clinical course of CD. Furthermore, the development of specific therapies would benefit from an improved mechanistic understanding of the pathogenesis of the disease.
Research objectives
The aim of this study was to identify disease-specific gene expression profiles of PBMCs from patients with CD in clinical remission. Specifically, we were interested in alterations of the gene expression profile after challenging PBMCs with pathogen-associated molecular patterns (PAMPs) and the immunomodulatory hormone vitamin D.
Research methods
PBMCs from patients with CD and healthy donors were cultured with vitamin D, peptidoglycan (PGN) and lipopolysaccharide (LPS), before RNA was isolated and subjected to microarray analysis and quantitative real-time PCR. Disease-specific gene expression profiles were evaluated by general linear model repeated measure analysis, paying particular attention to the well-established CD risk gene NOD2.
Research results
Microarray experiments yielded a total of 267 genes that were significantly up- or downregulated in PBMCs of patients with CD, compared to healthy donors, after challenge with vitamin D and/or a combination of LPS and PGN. For further analysis by real-time PCR, genes with roles in inflammation and immunity were selected. For three of these genes, CLEC5A, lysozyme and TREM1, a disease-associated expression pattern was validated. Six genes, including CLEC5A and lysozyme, were found to be expressed in a NOD2-dependent manner.
Research conclusions
PBMCs of patients with CD display alterations of their response to vitamin D and PAMPs that are preserved even at the stage of clinical remission. CLEC5A, TREM1 and NOD2 may act in a common network relevant to CD pathogenesis.
Research perspectives
Follow-up studies on alterations of the antipathogenic immune response may provide novel insights into the pathogenesis of CD and may also help to establish biomarkers to better predict the clinical course of the disease.
