Two new findings might clear a path to better treatment for eosinophilic esophagitis
Research reported online in July in Nature Genetics identifies a new genetic and molecular pathway in the esophagus that causes eosinophilic esophagitis (EoE).
EoE, a chronic inflammatory disorder of the esophagus, is triggered by allergic hypersensitivity to certain foods and an accumulation of eosinophils (white blood cells) in the esophagus. It causes gastrointestinal distress, difficulty swallowing, tissue scarring, fibrosis, strictures and other medical complications.
A team of researchers, led by Marc Rothenberg, MD, PhD, Director of the Division of Allergy and Immunology and the Center for Eosinophilic Disorders, and John Harley, MD, PhD, of the Center for Autoimmune Genomic Etiology, identified a molecular pathway specific to epithelial tissue in the esophagus that involves a gene called calpain14 (CAPN14). The gene becomes dramatically up-regulated in the disease process. The researchers attribute the up-regulation to the immune hormone Interleukin 13 (IL-13), a well-known molecular activator of EoE. Because CAPN14 can be inhibited by drugs, the study opens up new therapeutic possibilities, say the researchers.
In another finding for EoE, the results of a clinical trial led by Rothenberg published in August 2014 in Gastroenterology showed that high doses of the corticosteroid fluticasone propionate halted the inflammation of eosinophilic esophagitis (EoE) in a number of people. Some trial participants did not respond to fluticasone, however, even after six months of high-dose treatments, providing evidence that certain people with EoE are steroid-resistant. By analyzing gene expression in esophageal tissues, the scientists identified a cluster of genes that may help predict steroid responsiveness. The study was funded by the National Institute of Allergy and Infectious Diseases.