Tissue-specific microRNA signatures in pediatric inflammatory bowel disease with juvenile idiopathic arthritis: differential expression and cross-platform evaluation

Background & AimDevelopment of extraintestinal manifestations in pediatric inflammatory bowel disease (pIBD) is associated with a more severe disease course; juvenile idiopathic arthritis (JIA) is the most frequent extraintestinal manifestation in pIBD. We investigated whether intestinal mucosal microRNAs measured at pIBD diagnosis could predict subsequent JIA (pIBD-JIA) before symptoms emerge. MethodsWe analyzed formalin-fixed, paraffin-embedded diagnostic intestinal biopsies from 101 pediatric patients under 18 years of age: a discovery cohort (n=62; 27 pIBD, 25 pIBD-JIA, 10 non-IBD controls) and a validation cohort (n=39; 29 pIBD, 10 non-IBD; pIBD-JIA cases reused from discovery cohort). Discovery profiling used Affymetrix GeneChip miRNA 4.0. Significant probe sets were cross-referenced in MirGeneDB 2.1 and literature-curated to nominate candidates for RT-qPCR validation. ResultsWe identified 532 differentially expressed probe sets across groups (adjusted p<0.05); 123 microRNAs showed absolute log2 fold change >2. Thirteen microRNAs exhibited the clearest separation between pIBD and pIBD-JIA; 11 achieved AUC>0.70 in discovery. Four candidates (miR-663a, miR-3197, miR-4463, miR-92a-3p) were advanced to RT-qPCR validation. Two assays (miR-3197, miR-4463) failed technical criteria; differences in miR-663a and miR-92a-3p were reproduced within a discovery subset but did not replicate in the pIBD/non-IBD validation cohort. ConclusionsDiagnostic mucosal microRNA profiles distinguished pIBD patients who later developed JIA in discovery, but selected microRNA candidates were not general across cohorts. These findings underscore both the potential of tissue microRNAs as prognostic markers and the need for larger, fully independent, standardized studies before clinical translation.