834 Ileal Transcriptome Analysis Reveals Mucosal Immune Maturation With Increasing Age-of-Onset in Pediatric Crohn Disease and Healthy Controls - A Mucosal Gene Expression Based Signature That Supports the Paris Classification for Age-of-Onset

Abstract

matched controls without IBD. Information including diagnosis, IBD type, IBD activity, IBD medications, proton pump inhibitor (PPI) use, hospitalizations and antibiotic use was recorded. Patients were followed with repeat fecal and serum samples obtained. Cytotoxic culture for CD along with PCR to detect the toxin B gene was conducted on stool. Pulsed field gel electrophoresis (PFGE) was performed to determine strain type. Enzyme-linked Immunosorbent Assay (ELISA) was used to determine immunoglobulin G, A andM responses to CD toxin A and B from serum. Results: The prevalence of CD carriage was significantly greater in patients with IBD (17%) compared with controls (3%) (p=0.012). PCR to detect the toxin B gene compared to the gold standard of cytotoxic culture had a sensitivity of 92% and specificity of 100%. No patients showed clinical evidence of active CD infection. Among patients with IBD, IBD type, disease activity, IBD therapy, antibiotic use and hospitalizations were not found to be associated with CD carriage. PPI use was significantly more frequent in patients with CD carriage (54% vs. 25%, p,0.05). PFGE identified 6 different North American Pulsed Field Type (NAP) strains that then varied over time. There was a significantly greater proportion of patients with a positive antibody response to toxin A with IBD (69%) vs. controls (53%) (p,0.05), with a parallel trend of increased IgG and IgA responses against both toxin A and toxin B in those with IBD. Conclusions: Our findings show that asymptomatic toxigenic CD carriage, likely acquired in the community, is increased in pediatric IBD outpatients compared with controls. A variety of NAP strains were identified and these changed over time in CD colonized patients. PPI use was associated with an increased risk of carriage. Antibody responses of patients with IBD to CD toxins were increased, potentially promoting asymptomatic colonization. Future studies are needed to identify risk factors for symptomatic CD in pediatric IBD.