Maria Dorn-Rasmussen

Background & Aim: Development 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. Methods: We 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. Results: We identified 532 differentially expressed probe sets across groups (adjusted p2. 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. Conclusions: Diagnostic 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.

Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.

Background: Incidence rates of inflammatory bowel disease [IBD] reported from developed countries are rising, with some levelling out. The aim of this study was to assess the disease burden of IBD by estimating the incidence and prevalence across age groups and projecting these to 2030 in a high-incidence country.Methods: Using an algorithm [incorporating ICD codes, medications and histopathology], patients [n = 69 862] diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC] between 1980 and 2017 were identified in the Danish National Patient Registry and included in a nationwide cohort.Results: From 1980 to 2017 the overall incidence of CD increased from 5.1 [95% CI: 4.5–5.8] to 15.6 [95% CI: 14.6–16.6] per 100 000, while the incidence of UC increased from 6.2 [95% CI: 5.5–6.9] to 27.2 [95% CI: 25.9–28.6] per 100 000. For paediatric-onset CD [pCD], the incidence increased from 1.9 [95% CI: 1.2–2.8] to 9.9 [95% CI: 8.1–11.8] per 100 000 and from 1.8 [95% CI: 1.2–2.8] to 8.7 [95% CI: 7.1– 10.5] per 100 000 for paediatric-onset UC [pUC]. In 2017, the prevalence of CD and UC was 293 [95% CI: 288–297] and 523 [95% CI: 517–528] per 100 000. For pCD and pUC, the prevalence was 35 [95% CI: 31–38] and 28 [95% CI: 26–32] per 100 000.Conclusions: The incidence of paediatric- and adult-onset IBD in Denmark continues to increase and is among the highest in the world.