Published online: January 16, 2017
Allergy involves inappropriately strong immune responses towards otherwise harmless foreign proteins (“allergens”). These responses occur in part due to immune cells receiving increased exposure to allergens when epithelial barriers lose their structural integrity. However, it is not known why the allergic inflammation manifests in different organs for individual patients—lungs, skin, and esophagus for patients with asthma, atopic dermatitis, and eosinophilic esophagitis (EoE), respectively—when all have systemic sensitization to the triggering allergens.
A prominent advance within the last few years has been the identification of genes that are expressed specifically in particular organs. In a study recently published in The Journal of Allergy & Clinical Immunology (JACI), Rochman and colleagues utilized esophagus-specific genes identified by The Human Protein Atlas Project to assess the potential role of organ-specific genes in allergy. They characterized the expression of these esophagus-specific genes in esophageal biopsy specimens of patients with EoE, a chronic, inflammatory, food allergen–driven disorder.
Of the 297 esophagus-specific genes, the researchers found that 39% of them had altered expression in EoE, with 90% having decreased expression. Altered expression was more common in genes involved in epithelial differentiation and regulation of protease activity. Correspondingly, analysis of esophageal biopsy specimens revealed a profound loss of differentiation within the esophageal epithelium. After modelling the esophagus by growing esophageal epithelial cells in a three-dimensional culture system, the alterations in gene expression were reproduced by exposing the developing epithelial layers to interleukin 13, an allergy-promoting cytokine known to be a driver of EoE. Notably, the authors found rare mutations in esophagus-specific genes in patients with EoE.
The authors conclude that the pathogenesis of EoE involves a loss of tissue identity within the esophagus as there is a loss of epithelial differentiation and striking alterations in esophagus-specific genes. These results build upon a previous finding that the gene with the strongest association with EoE disease risk, CAPN14, encodes an esophagus-specific protease. The authors propose that the loss of tissue identity may help explain the organ specificity of EoE and potentially other allergic diseases.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI and is the most-cited journal in the field of allergy and clinical immunology.