Transcriptomic Evaluation of Skin Tape-strips in Children with Allergic Asthma Uncovers Epidermal Barrier Dysfunction and Asthma-associated Biomarkers Abnormalities

Overview

Journal Allergy

Specialty Allergy & Immunology

Date 2024 Feb 20

PMID 38375886

Authors

Ester Del Duca

Dante Dahabreh

Madeline Kim

Jonathan Bar

Joel Correa Da Rosa

Grace Rabinowitz

Paola Facheris

Pedro Jesus Gomez-Arias

Annie Chang

Vivian Utti

Amira Chowdhury

Ying Liu

Yeriel D Estrada

Alexandru Laculiceanu

Ioana Agache

Emma Guttman-Yassky

Affiliations

Soon will be listed here.

Abstract

Introduction: Tape-strips, a minimally invasive method validated for the evaluation of several skin diseases, may help identify asthma-specific biomarkers in the skin of children with allergic asthma.

Methods: Skin tape-strips were obtained and analyzed with RNA-Seq from children with moderate allergic asthma (MAA) (n = 11, mean age 7.00; SD = 1.67), severe allergic asthma (SAA) (n = 9, mean age 9.11; SD = 2.37), and healthy controls (HCs) (n = 12, mean age 7.36; SD = 2.03). Differentially expressed genes (DEGs) were identified by fold change ≥2 with a false discovery rate <0.05. Transcriptomic biomarkers were analyzed for their accuracy in distinguishing asthma from HCs, their relationships with asthma-related outcomes (exacerbation rate, lung function-FEV1, IOS-R5-20, and lung inflammation-FeNO), and their links to skin (barrier and immune response) and lung (remodeling, metabolism, aging) pathogenetic pathways.

Results: RNA-Seq captured 1113 in MAA and 2117 DEGs in SAA. Epidermal transcriptomic biomarkers for terminal differentiation (FLG/filaggrin), cell adhesion (CDH19, JAM2), lipid biosynthesis/metabolism (ACOT2, LOXL2) were significantly downregulated. Gene set variation analysis revealed enrichment of Th1/IFNγ pathways (p < .01). MAA and SAA shared downregulation of G-protein-coupled receptor (OR4A16, TAS1R3), upregulation of TGF-β/ErbB signaling-related (ACVR1B, EGFR, ID1/2), and upregulation of mitochondrial-related (HIGD2A, VDAC3, NDUFB9) genes. Skin transcriptomic biomarkers correlated with the annualized exacerbation rate and with lung function parameters. A two-gene classifier (TSSC4-FAM212B) was able to differentiate asthma from HCs with 100% accuracy.

Conclusion: Tape-strips detected epithelial barrier and asthma-associated signatures in normal-appearing skin from children with allergic asthma and may serve as an alternative to invasive approaches for evaluating asthma endotypes.

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