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Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
Published on: June 2, 2023
Inflammation significantly alters mucosal transcriptomic signatures in pediatric inflammatory bowel disease
Alexander Schnell1, Xinyi Wei1,2, Jan Bossenz3
1Pediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Insights
The IBD-DCA score effectively assesses pediatric inflammatory bowel disease (IBD) activity. Inflammation severity, not disease type, significantly impacts gene expression in pediatric IBD patients.
Area of Science:
- Gastroenterology
- Pediatric Inflammatory Bowel Disease (IBD)
- Molecular Biology
Background:
- Crohn's disease (CD) and ulcerative colitis (UC) share inflammatory features, particularly in children.
- Existing histopathological scoring systems are often specific to either CD or UC.
- The IBD-DCA score integrates both CD and UC into a single system but requires validation in pediatric populations.
Purpose of the Study:
- To validate the IBD-DCA scoring system in pediatric IBD patients.
- To investigate the relationship between inflammation severity and gene expression profiles in pediatric IBD.
- To identify key genes associated with inflammation in pediatric IBD.
Main Methods:
- Retrospective analysis of gene expression data from 25 pediatric IBD patients (16 CD, 9 UC).
- Application of the IBD-DCA score by an experienced pathologist to assess inflammation.
- Stratification of patients into low (0-3) and high (4-6) DCA score groups.
- Differential gene expression (DEG) analysis between low and high inflammation groups.
Main Results:
- The IBD-DCA score successfully stratified inflammation in pediatric CD and UC.
- DEG analysis identified 130 upregulated genes in the high inflammation group.
- Eleven hub genes involved in immune regulation, including cytokines and costimulatory receptors, were identified.
Conclusions:
- Inflammatory activity, as measured by the IBD-DCA score, significantly influences the transcriptomic signature in pediatric IBD.
- The IBD-DCA score is a valuable tool for assessing inflammation in pediatric IBD.
- Gene expression patterns are more closely linked to inflammation severity than the specific disease entity (CD vs. UC).
Objectives And Study:
Crohn's disease (CD) and ulcerative colitis (UC) share common features of inflammation to a greater extent in children than in adults. However, histopathological scoring systems of mucosal inflammation are usually available only for either one of these entities. The IBD-DCA score is the first of its kind to incorporate both into one scoring system but still lacks validation in pediatric IBD.
Methods:
An existing data of a multiplexed gene expression analysis of mucosal biopsies of 25 patients diagnosed with either CD (n = 16) or UC (n = 9) were evaluated according to the IBD-DCA score for distribution (D0-2), chronicity (C0-2) and activity (A0-2) of inflammation by an experienced pathologist. The scoring results were used to stratify the degree of mucosal inflammation of these patients into either low (0-3) or high (4-6) DCA scores. Subsequently, analysis for differentially expressed genes (DEG) between the low and high inflammation group was performed.
Results:
Scoring revealed 7 low and 9 high DCA samples for CD, whereas for UC only high DCA were scored. DEG analysis revealed 130 upregulated genes in the high DCA group compared to the low DCA group. 11 genes were identified as hub genes playing a pivotal role in immune regulation, among those several cyto- or chemokines (IL1B, CCL20, CXCL1/2), costimulatory receptors (IL2RA, CD80, TLR2) and modulatory proteins like PD-L1 and IDO1.
Conclusion:
Our results indicate that inflammatory activity rather as assessed by the IBD-DCA score rather than the underlying disease entity significantly alters the transcriptomic signature in mucosal specimens of pediatric IBD patients.
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