Researchers report that they have discovered the cause of eosinophilic esophagitis (EoE), a hard-to-treat food allergy. In EoE, large numbers of white blood cells, known as eosinophils, accumulate in the lining of the esophagus (the tube that connects the mouth to the stomach), causing chronic inflammation. Led by a team at Cincinnati Children’s Hospital, investigators have found a new genetic and molecular pathway in the esophagus. This discovery, reported online today in Nature Genetics, opens the door to new therapies for EoE, which has been diagnosed in a growing number of children and adults over the past decade.
The study found that EoE is triggered by the interplay between epithelial cells, which help form the lining of the esophagus, and a gene called CAPN14. When the epithelial cells are exposed to an immune hormone called interleukin 13 (IL-13), which is known to play a role in EoE, they cause a dramatic increase in CAPN14. CAPN14 encodes an enzyme called calpain14, which is also part of the disease process. Because drugs can target calpain 14 and modify its activity, the study opens up new therapeutic strategies for researchers to explore.
“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,” says Marc E. Rothenberg, MD, senior investigator on the study. “This is a major breakthrough for this condition … Our results are immediately applicable to EoE and have broad implications for understanding eosinophilic disorders as well as allergies in general.” The study was funded, in part, by the National Institutes of Health (NIH), with additional support from other organizations, including FARE.