Inflammation significantly alters mucosal transcriptomic signatures in pediatric inflammatory bowel disease.

[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 ( = 16) or UC ( = 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.