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Study finds cause of mysterious food allergy, suggests new treatment strategy
Date:7/13/2014

New research in Nature Genetics identifies a novel genetic and molecular pathway in the esophagus that causes eosinophillic esophagitis (EoE), opening up potential new therapeutic strategies for an enigmatic and hard-to-treat food allergy.

EoE is a chronic inflammatory disorder of the esophagus. The condition is triggered by allergic hypersensitivity to certain foods and an over-accumulation in the esophagus of white blood cells called eosinophils (part of the body's immune system). EoE can cause a variety of gastrointestinal complaints including reflux-like symptoms, vomiting, difficulty swallowing, tissue scarring, fibrosis, the formation of strictures and other medical complications.

Reporting their results online, the multi-institutional team of researchers was led by scientists at Cincinnati Children's Hospital Medical Center. The authors identified a molecular pathway specific to epithelial tissue in the esophagus involving a gene called CAPN14, which they found becomes dramatically up-regulated in the disease process.

Epithelial cells help form the membrane of the esophagus. The scientists report that when these cells were exposed to a well-known molecular activator of EoE an immune hormone called Interleukin 13 (IL-13) it caused dramatic up-regulation of CAPN14. The researchers said this happened in what they described as an epigenetic hotspot for EoE on the cells' chromosomes.

CAPN14 encodes an enzyme in the esophagus that is part of the disease process called calpain14, according to Marc E. Rothenberg, MD, senior investigator on the study and director of the Center for Eosinophilic Disorders at Cincinnati Children's. Because caplain14 can be targeted and inhibited by drugs, the study opens up new therapeutic strategies for researchers.

"In a nutshell, we have used cutting edge genomic analysis of patient DNA as well as gene and protein analysis to explain why people develop EoE," Rothenber
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Contact: Jim Feuer
jim.feuer@cchmc.org
513-636-4656
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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