Integrative skin-blood transcriptomic analysis identifies circulating biomarkers reflecting disease activity in atopic dermatitis.

Atopic dermatitis (AD) is characterized by complex immune dysregulation primarily studied in lesional skin. Identifying circulating molecular signatures that mirror cutaneous inflammation could enable non-invasive disease monitoring. Transcriptomic data from lesional skin and peripheral blood T lymphocytes of patients with AD were analyzed using differential expression, pathway enrichment, upstream regulator prediction, and protein-protein interaction network modeling. Genes dysregulated in both compartments were prioritized and validated in serum samples from patients with moderate-to-severe AD. Despite limited concordance at the individual gene level, skin and blood shared a common inflammatory regulatory landscape, including activation of Th2- and Th17-related cytokine signaling, together with a consistently prediction of ESR1 inhibition across both compartments. Network analysis identified key hub genes and a neuro-immune signaling module. Among shared molecules, serum S100A8 levels positively correlated with disease severity, while SOCS3 showed a negative association. LCN2 and CTLA4 displayed trends toward correlation. Systemic molecular alterations in AD partially reflect cutaneous inflammation and support circulating S100A8 and SOCS3 as potential biomarkers of disease activity.