In what could open up potential new therapeutic strategies for a hard-to-treat food allergy, researchers have discovered that a novel genetic and molecular pathway in the foodpipe (esophagus) causes the disease.
"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 (eosinophillic esophagitis)," said Marc Rothenberg from Cincinnati Children's Hospital Medical Center in the US.
Triggered by allergic hypersensitivity to certain foods, EoE can cause a variety of gastrointestinal complaints, including reflux-like symptoms, vomiting, difficulty in swallowing, tissue scarring, fibrosis, the formation of strictures and other medical complications.
Over-accumulation in the esophagus of white blood cells called eosinophils (part of the body's immune system) may also lead to EoE, a chronic inflammatory disorder of the esophagus.
The researchers 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.
CAPN14 encodes an enzyme in the esophagus that is part of the disease process called calpain14 and because caplain14 can be targeted and inhibited by drugs, the study opens up new therapeutic strategies for researchers.
"This is a major breakthrough for this condition and gives us a new way to develop therapeutic strategies by modifying the expression of caplain14 and its activity," Rothenberg said.
The researchers used computer bioinformatics to conduct a genome-wide association study that analysed 2.5 million genetic variants in thousands of individuals with and without EoE.
This allowed the authors to identify the genetic susceptibility within the CAPN14 gene.
The study appeared in the journal Nature Genetics.
