Oral

Introduction & objectives:
ess invasive serologic testing for Crohn’s disease (CD) may be valuable in pediatric patients, particularly given the association between serum immune reactivity and severe disease phenotypes that is drawing increasing attention. This study aimed to determine whether the methylation signature of peripheral blood at diagnosis could predict the presence of complicated phenotype in pediatric CD patients.

Methods:
In order to identify the key differentially methylated regions (DMRs) driving complicated phenotype in pediatric CD, bioinformatics analyses were performed based on the Gene Expression Omnibus database (GSE112611). Limma and DMRcate were employed to identify differentially methylated probes and regions. The MethylationEPIC genome-wide methylation analysis was performed using the R statistics program.

Results:
We identified 4215 sites that were significantly differentially methylated when comparing stricturing and inflammatory pediatric patients with CD. Of these, 58 DMRs mapped to GNAS gene, 23 DMRs mapped to RNF39 gene, and 23 DMRs mapped to HLA-L gene with respect to the complicated phenotype. We also show that differential variability selects features with heterogeneous outlier methylation profiles and that these play a key role in the complicated phenotype at diagnosis in pediatric CD.

Conclusion:
Our results, which provide a comprehensive analysis of DNA methylation profiling in blood of pediatric patients with CD, suggest that its peculiar dynamicity can be relevant for complicated phenotype in response to the environment factor. In addition, the GNAS, RNF39, and HLA-L gene signatures could be candidate blood biomarkers to identify the complicated phenotype for pediatric patients with CD at diagnosis. Further studies are needed to validate this hypothesis.