title: Analysis and expansion of the eosinophilic esophagitis transcriptome by RNA sequencing.
abstract: 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.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Sherrill
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Kiran
authors.affiliation: Nutrition and Health/Allergy Group, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Blanchard
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Stucke
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Kemme
authors.affiliation: Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Collins
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Abonia
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Putnam
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Mukkada
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kaul
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Kocoshis
authors.affiliation: Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Kushner
authors.affiliation: Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Plassard
authors.affiliation: Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Karns
authors.affiliation: Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Dexheimer
authors.affiliation: Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Aronow
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D057765:Eosinophilic Esophagitis / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D034622:RNA Interference; D022661:RNA, Untranslated / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA / Q000379:methods*; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D018793:Interleukin-13; D022661:RNA, Untranslated