Transcriptomic evaluation of skin tape-strips in children with allergic asthma uncovers epidermal barrier dysfunction and asthma-associated biomarkers abnormalities.
Allergy
; 79(6): 1516-1530, 2024 06.
Article
en En
| MEDLINE
| ID: mdl-38375886
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-ß/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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Asma
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Biomarcadores
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Perfilación de la Expresión Génica
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Transcriptoma
Límite:
Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Año:
2024
Tipo del documento:
Article