Phenotype of Atopic Dermatitis with Food Allergy Predicts Development of Childhood Asthma via Gut Wnt Signaling

Abstract

Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a wide spectrum of clinical phenotype. However, specific description of phenotypes of AD depending on the comorbidities in early childhood is lacking. This study aimed to investigate whether the AD phenotype in early childhood is related to childhood asthma and to elucidate the mechanisms involved. Methods: Data on the first 3 years of life were collected prospectively from 1,699 children in the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). We applied an unsupervised latent class analysis to the following five factors: food sensitization, inhalant sensitization, food allergy (FA), AD, and recurrent wheezing. The risks of developing FA, AD, allergic rhinitis (AR), and asthma in children aged 5–7 years were evaluated. Colonocyte transcriptome and ingenuity pathway analysis were performed. Results: Four phenotypes were identified; no allergic diseases (78.4%), AD without sensitization (16.4%), FA with AD (2.9%), and AD with sensitization (7.8%). The FA with AD had the highest risk for FA, AR, and asthma and the highest cord blood immunoglobulin E (IgE) levels. In AD without sensitization and with sensitization, scoring of AD (SCORAD) in early childhood was higher than in FA with AD. Canonical pathway analysis with the colonocyte transcriptome revealed that the key pathway in FA with AD was ‘Wnt/β-catenin Signaling.’ The relative abundance of Wnt6 mRNA was positively correlated with food-specific IgE levels at 1 and 3 years. Conclusions: When FA is present in various phenotypes of AD at early life, regardless of severity of eczema, it may be associated with gut Wnt signaling and later development of asthma.