Tape strip transcriptomic analysis of Thai patients with atopic dermatitis shows greater immune and barrier abnormalities in the setting of comorbid food allergy

Summary: Abstract Body: Atopic dermatitis(AD) and food allergy(FA), both in the atopic march, commonly co-occur, and may share immune and barrier abnormalities. Studies show that FA may exacerbate AD and induce changes in the skin barrier and microbiome. Using tape strip transcriptomics, we aim to compare the molecular features of a pediatric Thai moderate AD cohort with and without comorbid food allergy. Tape strips were collected and analyzed via RNAseq from the lesional(LS) and nonlesional (NL) skin in a Thai cohort of children with AD+FA (n=17), AD only (n=12), and from healthy controls (HC) (n=8). Differentially expressed genes (DEGs) were defined by fold change>1.5 and false discovery rate<0.05. While all AD patients showed immune and barrier alterations compared to HC in both LS and NL skin, FA exacerbated the inflammatory tone in LS skin, with 1,260 DEGs (638up/622down) in the AD+FA group vs 600 DEGs (277up/323down) in AD only. Markers of innate immunity (IL1B/IL6), Th2 (CCL13/CCL24/IL10), and Th1 (CXCL10/MX1) showed stronger upregulation in AD+FA. Th17 skewing, associated with Asian and pediatric AD, was universal, but especially pronounced in AD+FA (IL17A/IL-17F/CXCL1), while Th22 (IL22/S100A8/9) was higher in AD only. Barrier dysfunction was higher in AD+FA, with greater attenuation in genes associated with terminal differentiation (FLG/LCE1B/2A) and tight junctions (CLDN8). Significant increases in key markers of pruritus (IL-31), interferon (IFIT1/44), histamines (HRH4/HDC), mast cells (CPA3), and eosinophils (RNASE2) were also uniquely seen in AD+FA, but not AD only. We demonstrate that the immune and barrier dysregulation in AD worsen in the setting of concomitant FAs, which may drive more severe and persistent AD disease. The presence of FA may define a distinct AD endotype, warranting more aggressive immune targeting approaches to control higher inflammation. Daniel Liu¹, Panipak Temboonnark^{1, 2, 3}, Ester Del Duca¹, Yeriel Estrada¹, Helen He¹, Emma Guttman-Yassky¹ 1. Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 2. Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, Thailand. 3. Medicine, Rangsit University, Bangkok, Thailand. Translational Studies: Preclinical