Scientists have found the cause of a chronic inflammatory disorder of the esophagus, paving the way for new therapeutic strategies for an enigmatic and hard-to-treat food allergy.
Researchers have identified a novel genetic and molecular pathway in the esophagus that causes eosinophillic esophagitis (EoE).
EoE 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.
The multi-institutional team of researchers led by scientists at Cincinnati Children's Hospital Medical Center 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 reported 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, senior investigator on the study and director of the Center for Eosinophilic Disorders at Cincinnati Children's.
The findings open a new way to consider therapeutic options because calpain14 is an enzyme that can be inhibited by drugs, which means it may be possible to modify the expression and activity of calpain14.