Airway Epithelial Gene Expression Differs Across Urban Childhood Asthma Phenotypes
Altman M, Zoratti E, Liu A, Pongracic J, Gereige J, Wood R, Hershey GK, Kercsmar C, Gruchalla R, Kattan M, Teach S, Ylescupidez A, Sigelman S, Gergen P, Togias A, Visness C, Presnell S, Gern J, Busse W, and Jackson D. Airway Epithelial Gene Expression Differs Across Urban Childhood Asthma Phenotypes. J Allergy Clin Immunol 2021; 147(2):AB37.
J Allergy Clin Immunol
Rationale: Children living in low-income urban environments experience high asthma morbidity. Prior phenotyping of these children has identified a subgroup with low levels of allergy (T2-low) but highly symptomatic asthma. Assessment of the airway epithelium in these children can provide important mechanistic insights into disease pathogenesis.
Methods: We performed RNA-sequencing of nasal brush samples from 123 children in the Asthma Phenotypes in the Inner City (APIC) cohort. These children were previously clustered into 5 phenotypes according to metrics of T2 biomarkers, lung function, rhinitis and asthma symptoms, and asthma severity. Differential gene expression was assessed by modular analysis.
Results: The cluster of children characterized by T2-low highly-symptomatic asthma and rhinitis had significantly increased expression of a module of 875 genes. This module was highly enriched for Neuroactive ligand-receptor interaction genes (KEGG; FDR=2.3E-5), Olfactory transduction genes (KEGG; FDR=2.6E-4) and Extracellular matrix genes (UniProtKB; FDR=8.6E-12), the latter of which included multiple collagen and ADAM (a disintegrin and metalloproteinase) genes. This expression module also included a small number of cytokine/receptor pathway genes notable for IL23R, IL26, and IL2 and an absence of canonical T2 genes. This pathway was upregulated 1.5-fold over the cluster of children with T2-low mild asthma, and 2.4-fold over the cluster of children with highly symptomatic T2-high asthma (FDRs <0.05).
Conclusions: Our results demonstrate a unique nasal gene expression profile characteristic of urban children with highly symptomatic asthma and rhinitis but with minimal allergy, most notable for numerous genes related to neuronal signaling and components of Th17 signaling, suggesting unique molecular mechanisms of disease.