P0255 Predictive potential of microRNA expression for Juvenile Idiopathic Arthritis development in paediatric Inflammatory Bowel Disease
Authors: Dorn-Rasmussen M , James J P , Malham M , Burisch J , Ingels H A S , Riis L B , Wewer V 
Published: January 2025

Abstract

Background
Children diagnosed with inflammatory bowel disease (IBD) often experience a more severe disease course than adults, and up to 50% develop extra-intestinal manifestations (EIMs).1 The most common EIM is juvenile idiopathic arthritis (JIA), affecting approximately 16–33% of paediatric patients with IBD, increasing risks of long-term complications such as uveitis, joint destruction, reduced physical activity, and psychological challenges.2 MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression and play key roles in immune and inflammatory processes. They hold potential as biomarkers and therapeutic targets in IBD, offering opportunities for advancements in early diagnosis and treatment.3
The aim of this study was to investigate whether miRNA expressed in intestinal biopsies can identify paediatric patients with IBD at risk of developing JIA.

Methods
Paediatric patients under 18 years of age diagnosed with IBD between 1 May 2021 and 1 May 2024, along with healthy controls from the Copenhagen IBD Inception Cohort, were enrolled.4 One mucosal biopsy from either the ileum or colon was collected from each patient during their index endoscopy. Additionally, biopsies from paediatric patients diagnosed with both IBD and JIA (IBD-JIA) prior to 1 May 2021 were retreived from the Department of Pathology at Copenhagen University Hospital, Hvidovre. Total RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue, and miRNA expression was analysed using the GeneChip™ microarray platform.

Results
The study included 62 biopsies from 62 patients (27 with IBD, 25 with both IBD and JIA (IBD-JIA), and 10 HC). Patient characteristics are shown in table 1. Analysis identified 532 significantly differentially expressed probe sets (adjusted p&lt;0.05) among IBD, IBD-JIA, and HC (Figure 1). Among these, 123 probe sets, including miR-486-2, let-7b-5p, and miR-92a-3p, exhibited a more than two-fold change (adjusted p&lt;0.001) between IBD and IBD-JIA, with 120 miRNAs upregulated and 3 downregulated in IBD-JIA compared to IBD.

Conclusion
This study provides the first evidence of differential miRNA expression in paediatric patients with IBD and co-occurring JIA. These miRNAs may serve as novel biomarkers for the early detection, aiding in timely diagnosis and better management of paediatric IBD patients.

References
1.Gordon H, Burisch J, Ellul P, et al. ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis. 2024;18(1):1-37. doi:10.1093/ecco-jcc/jjad108
2.Cardile S, Romano C. Current issues in pediatric inflammatory bowel disease-associated arthropathies. World J Gastroenterol. 2014;20(1):45-52. doi:10.3748/wjg.v20.i1.45
3.Alfaifi J, Germain A, Heba AC, et al. Deep Dive Into MicroRNAs in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2023;29(6):986-999. doi:10.1093/ibd/izac250
4.Attauabi M, Madsen GR, Bendtsen F, et al. Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study): the protocol for a Copenhagen IBD Inception Cohort Study. BMJ Open. 2022;12(6). doi:10.1136/bmjopen-2021-055779