Study Discovers Cause of EoE Food Allergies
A new study has found the genetic and molecular relationship that causes eosinophilic esophagitis (EoE). It’s a discovery that could lead to new therapies for the notoriously difficult-to-manage disease.
“This is a major breakthrough for this condition,” said Dr. Marc Rothenberg, senior investigator of the multi-center study and director of the Center for Eosinophilic Disorders at the Cincinnati Children’s Hospital. “Our results are immediately applicable to EoE and have broad implications for understanding eosinophilic disorders as well as allergies in general.”
EoE is a chronic inflammatory condition that’s characterized by high accumulations in the esophagus of white blood cells called eosinophils, as well as hypersensitivity to certain foods. (And in many patients, that’s to a great numbers of foods.) EoE is considered a form of food allergy.
The study, published online in Nature Genetics, centers around a gene called CAPN14. This gene encodes an enzyme, called calpain 4, which plays a role in the disease process of EoE and can be found in the epithelial cells that line the esophagus.
When these epithelial cells are exposed to the immune hormone IL-13 (a known trigger of EoE), it causes dramatically increased activity of CAPN14. Thus, the study demonstrates that in order for EoE to manifest, “two steps are necessary, one dictated by allergy and one dictated by calpain14 in the esophagus,” says Rothenberg.
This discovery means the scientists will now be seeking new therapies to target the enzyme produced by CAPN14 .
“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,” said Rothenberg. “This is a major breakthrough for this condition and gives us a new way to develop therapeutic strategies by modifying the expression of calpain14 and its activity.”
The researchers used a sophisticated computer process to analyze 2.5 million genetic variants in thousands of individuals with and without EoE. This led them to the genetic susceptibility within CAPN14. The investigators were surprised to learn that CAPN14 was specifically expressed in the esophagus, compared with 130 other tissues in the body they had analyzed.
See also: EoE: When Food Becomes Foe