Differential Expression of Proteins Involved in Skin Barrier Maintenance and Vitamin D Metabolism in Atopic Dermatitis: A Cross-Sectional, Exploratory Study

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by proteins involved in skin barrier maintenance and vitamin D metabolism. Using an intra-patient design, this study compared protein expression in intra-lesional (IL) and peri-lesional (PL) skin biopsies from AD patients and examined associations between protein levels, vitamin D status, and clinical features. Forty-four biopsies from twenty-two AD patients were analyzed using antibody microarrays targeting twelve proteins. IL samples had significantly higher total protein levels than PL samples, with a mean difference of 77.7% (<i>p</i> < 0.001). Several proteins, including cathelicidin, cingulin, occludin, filaggrin, and the vitamin D receptor, were upregulated in IL samples. Patients with vitamin D levels below 30 ng/mL showed higher expression of CYP24A (<i>p</i> = 0.054), alpha-catenin (<i>p</i> = 0.043), and haptoglobin (<i>p</i> = 0.033). Increased EASI scores (≥16) were associated with elevated expression of CYP24A (<i>p</i> = 0.024), CYP27B (<i>p</i> = 0.044), filaggrin (<i>p</i> = 0.027), occludin (<i>p</i> = 0.049), and claudin-1 (<i>p</i> = 0.052). Multivariate regression analysis identified significant correlations between protein expression, skin prick test positivity, and low vitamin D levels. These findings suggest that proteins related to epithelial barrier function and vitamin D metabolism are highly upregulated in IL skin regions, offering potential therapeutic targets for improving both skin barrier function and overall disease severity in AD patients.