1562 Molecular characterization of dupilumab use in atopic dermatitis and impact on allergen sensitivity testing

This study examined clinical and immunogenetic changes in 15 atopic dermatitis (AD) patients treated with dupilumab for 52 weeks. Patients were systemic therapy-naïve moderate-to-severe AD: Eczema Area Severity Index (EASI) ≥ 12, Investigator Global Assessment (IGA) 3, body surface area 10%. assessed at 12 visits endpoints received skin biopsies of lesional non-lesional baseline weeks 2, 4, 12. Bulk RNA sequencing (RNA-seq) was performed on all biopsies; a subset samples further analyzed by RNA-seq flow-sorted cell populations (CD8+, CD4+ T effector, regulatory cells) or single-cell RNA-seq. A allergen patch testing week 26. The average (SD) age 39.7 (13.6) years, 7/15 (46.7%) males. By Week mean EASI reduction 65.0% (21.9%), 12/15 (80.0%) achieved 50, 2/15 (13.3%) reached IGA 0/1. Early bulk data comparing AD found significant upregulation 521 genes (top: HRNR, KRT6C, CXCL1) downregulation 459 DGAT2L6, PM20D1). At observed CCL26 NTRK1 WIF1; the most significantly suppressed signaling pathways double-strand DNA repair via homologous recombination receptor complex signaling. Patch nine allergens (e.g., neomycin sulfate, budesonide) that displayed increased sensitivity 26 compared to baseline. Five linalool, nickel) displaying 2+ no longer yielded any reaction 26, suggesting may suppress certain hypersensitivity reactions. These results expand how use impacts cutaneous gene expression reactivity.