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Genes Immun. 2014 Sep;15(6):361-9. doi: 10.1038/gene.2014.27. Epub 2014 Jun 12.

Analysis and expansion of the eosinophilic esophagitis transcriptome by RNA sequencing.

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Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Nutrition and Health/Allergy Group, Nestlé Research Center, Lausanne, Switzerland.
Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.


Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder of the esophagus that is compounded by genetic predisposition and hypersensitivity to environmental antigens. Using high-density oligonucleotide expression chips, a disease-specific esophageal transcript signature was identified and was shown to be largely reversible with therapy. In an effort to expand the molecular signature of EoE, we performed RNA sequencing on esophageal biopsies from healthy controls and patients with active EoE and identified a total of 1607 significantly dysregulated transcripts (1096 upregulated, 511 downregulated). When clustered by raw expression levels, an abundance of immune cell-specific transcripts are highly induced in EoE but expressed at low (or undetectable) levels in healthy controls. Moreover, 66% of the gene signature identified by RNA sequencing was previously unrecognized in the EoE transcript signature by microarray-based expression profiling and included several long non-coding RNAs (lncRNA), an emerging class of transcriptional regulators. The lncRNA BRAF-activated non-protein coding RNA (BANCR) was upregulated in EoE and induced in interleukin-13 (IL-13)-treated primary esophageal epithelial cells. Repression of BANCR significantly altered the expression of IL-13-induced proinflammatory genes. Together, these data comprise new potential biomarkers of EoE and demonstrate a novel role for lncRNAs in EoE and IL-13-associated responses.

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