A novel mechanism for developing multiple allergic symptoms including severe atopic dermatitis, food allergy, asthma, and eosinophilic gastroenteritis, and a potential for development of molecular targeted drug

Abstract

Allergic diseases are recognised as "common diseases” caused by multiple factors including genetic predisposition and environmental factors. However, in some patients with allergic diseases, comprehensive genomic analyses such as whole-exome sequencing (WES) analysis have recently revealed a causative single gene, which might be a good target molecule for drug discovery. In our WES analysis, a diagnosis was made in 42% of patients with some allergic symptoms, suggesting that allergic diseases, which are “common diseases”, include monogenic diseases.

In this symposium, we will present a severe case with multiple allergic symptoms in which a novel causative gene, STAT6 was identified by WES analysis. The proband showed multiple allergic symptoms including severe atopic dermatitis, food allergy, asthma, and eosinophilic gastroenteritis. In vitro experiments demonstrated that the STAT6 variant acted in a constitutively active manner. The variant knocked-in mice tended to spontaneously develop dermatitis similar to human atopic dermatitis. We propose that an exaggerated STAT6 response is a novel mechanism of allergic symptoms, which is a good therapeutic target. This mechanism has been shown in subsequent papers and is being established as a new entity of allergic diseases. We will also discuss recent findings surrounding STAT6.