Skin tape strips identify age-specific immune, metabolic, and barrier dysregulation signatures in children, adolescents, and adults with allergic asthma

Abstract

Background: Allergic asthma pathogenesis encompasses systemic immune, metabolic, and epithelial barrier dysfunction; however, minimally invasive tools to longitudinally explore these processes remain limited.

Objective: We evaluated the potential of minimally invasive skin tape strips to capture age-specific immune, metabolic, and epithelial barrier dysregulation in children, adolescents, and adults with allergic asthma and their association with asthma-related outcomes.

Methods: We collected tape strips from healthy-appearing skin of patients with moderate or severe allergic asthma and age-matched controls. RNA sequencing and differential gene expression analyses were performed to identify unique and common asthma-associated immune and barrier genes across age groups. Gene set variation analyses, pathway enrichment, correlation with clinical outcomes, and biomarker classification using receiver operating characteristic analysis were conducted.

Results: Children demonstrated the greatest transcriptomic dysregulation, including robust downregulation of barrier-related genes (FLG, CDH19, JAM2), upregulation of oxidative phosphorylation genes (NDUFS4, COX15), and T1 immune skewing. Adolescents exhibited attenuated barrier and immune changes compared to children and adults, suggestive of a transitional state. Adults with severe asthma showed dominant type 2/type 17 skewing, metabolic suppression, and fewer barrier alterations compared to children. Several differentially expressed genes correlated with asthma outcomes: ENG and MUC4 with small airway resistance in children, and inflammatory coding genes (CD1C, IL3RA, CCL17) with annual exacerbation rates in adults. The two-gene classifiers HOXA5-KDM6B and PCGF1-SLC39A2 accurately distinguished asthmatic subjects from controls (area under the curve = 1.0), with olfactory receptors and immune-related genes uniquely classifying adolescent asthma patients.

Conclusions: Skin tape strips identify age-specific immune, epithelial barrier, and metabolic signatures in allergic asthma, offering a minimally invasive tool to explore disease mechanisms.

Keywords: Allergic asthma; disease endotypes; epithelial barrier; immune dysregulation; immune metabolism; tape strips.