PLX074213

GSE101794: Age-of-Onset Dependent Immune maturation in Pediatric Crohn Disease

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Purpose: To clarify the biological processes underlying variation in disease location and antimicrobial sero-reactivity across age-of onset in pediatric Crohn disease.; Methods: We characterize the ileal global pattern of gene expression using single-end, 50bp RNA-sequencing using the Illumina HiSeq2000 in 304 treatment-nave pediatric Crohn patients and non-IBD controls. Reads were quantified using Kallisto with Gencodev23 annotations. For all analyses, data were stratified by patient age-of-onset.; Results: Performing differential analysis of all reasonably-expressed transcripts (TPM>5 in 5 samples, with significance defined as FDR-corrected p-value<0.05 and fold change1.5), we identify a robust gene signature with higher expresison of an immune gene set in older patients (10 years at diagnosis) compared to younger patients (<10 years at diagnosis), and a decrease in expression of antimicrobial Paneth cell-derived -defensins.; Conclusion: We provide evidence for maturation of mucosal Th1 immune response and loss of epithelial antimicrobial -defensins with increasing age-of-onset. SOURCE: Rebekah Karns (Rebekah.Karns@cchmc.org) - Cincinnati Children's Hospital Medical Center