Gastrointestinal symptoms are common in children with autism spectrum disorder (ASD) and are often associated with mucosal inflammatory infiltrates of the small and large intestine. Although distinct histologic and immunohistochemical properties of this inflammatory infiltrate have been previously described in this ASDGI group, molecular characterization of these lesions has not been reported. In this study we utilize transcriptome profiling of gastrointestinal mucosal biopsy tissue from ASDGI children and three non-ASD control groups (Crohn's disease, ulcerative colitis, and histologically normal) in an effort to determine if there is a gene expression profile unique to the ASDGI group. Comparison of differentially expressed transcripts between the groups demonstrated that non-pathologic (normal) tissue segregated almost completely from inflamed tissue in all cases. Gene expression profiles in intestinal biopsy tissue from patients with Crohn's disease, ulcerative colitis, and ASDGI, while having significant overlap with each other, also showed distinctive features for each group. Taken together, these results demonstrate that ASDGI children have a gastrointestinal mucosal molecular profile that overlaps significantly with known inflammatory bowel disease (IBD), yet has distinctive features that further supports the presence of an ASD-associated IBD variant, or, alternatively, a prodromal phase of typical inflammatory bowel disease. Although we report qPCR confirmation of representative differentially expressed transcripts determined initially by microarray, these findings may be considered preliminary to the extent that they require further confirmation in a validation cohort.
Citation: Walker SJ, Fortunato J, Gonzalez LG, Krigsman A (2013) Identification of Unique Gene Expression Profile in Children with Regressive Autism Spectrum Disorder (ASD) and Ileocolitis. PLoS ONE 8(3): e58058. doi:10.1371/journal.pone.0058058
Editor: Wenhui Hu, Temple University School of Medicine, United States of America
Received: April 18, 2012; Accepted: January 31, 2013; Published: March 8, 2013
Funding: The authors are grateful to the Jane Botsford Johnson Foundation for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: AK served as an expert witness in the role of treating pediatric gastroenterologist in the Autism Omnibus Hearings of 2007. AK has also served as expert witness on behalf of children with ASD associated bowel disease in Child Protective Services legal actions.