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

Abstract

Allergic asthma pathogenesis encompasses systemic immune, metabolic, and epithelial barrier dysfunction; however, minimally invasive tools to longitudinally explore these processes remain limited. 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. 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. 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. Skin tape strips identify age-specific immune, epithelial barrier, and metabolic signatures in allergic asthma, offering a minimally invasive tool to explore disease mechanisms.