Immunological differences in atopic dermatitis across age groups: Insights from single-cell multi-omics

Summary: Abstract Body: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, characterized by dry skin, eczematous lesions, and severe itching. AD affects a significant portion of the population, with a prevalence of 2.7% to 20.1% in children and 2.1% to 4.9% in adults, posing substantial socio-economic burdens. The disease exhibits high heterogeneity in its clinical presentation and progression, varying by age, severity, and ethnicity. This study investigates immunological differences in AD across age groups using single-cell transcriptomic and cell surface proteomic analysis of peripheral blood mononuclear cells (PBMCs) from 31 AD patients—12 pediatric, 14 adult, and 5 geriatric—and age-, gender-, and race-matched healthy controls (HC). After quality control, approximately 217,000 cells were analyzed comprising 28 distinct immune cell types. Initial findings revealed that effector populations including CD14 monocytes, CD4 TEM, CD4 CTL, and CD8 TCM increased in cell proportion with age, whereas naïve populations, including CD4 naïve, CD8 naïve, and B naïve cells, decreased with age. Differential gene expression and pathway analyses, focused on CD14+ monocytes across pediatric, adult, and geriatric groups, revealed distinct age-dependent trends in inflammation and immune responses. Pro-inflammatory cytokines and chemokines such as IL1B, TNF, and CCL3 showed increased upregulation with older age, while interferon-stimulated genes were predominantly upregulated in pediatric patients, highlighting a stronger antiviral response in younger individuals. These findings provide early insights into the age-dependent molecular mechanisms of AD, linking immune system development to disease heterogeneity. By evaluating single-cell immune data, this study lays the foundation for identifying age-specific biomarkers and developing machine learning models of age-dependent AD, enabling more personalized treatment strategies for AD across the lifespan. Gian Carlo Baldonado¹, Sugandh Kumar¹, Joy Jin¹, Xiaohui Fang¹, Bobby Shih¹, Wilson Liao¹ 1. Dermatology, University of California San Francisco Department of Dermatology, San Francisco, CA, United States. Bioinformatics, Computational Biology, and Imaging