The proteomic skin profile of moderate-to-severe atopic dermatitis patients shows an inflammatory signature

Background: Moderate-to-severe atopic dermatitis (AD) is increasingly recognized as a systemic disease, largely due to proteomic blood studies. There are growing efforts to develop AD biomarkers using minimal tissues. Objective: To characterize the AD skin proteomic signature and its relationship with the blood proteome and genomic skin profile in the same individuals. Methods: We evaluated lesional and nonlesional biopsy samples and blood from 20 individuals with moderate-to-severe AD and 28 healthy individuals using Olink Proteomics (Uppsala, Sweden), using 10 μg/10 μL for skin and blood and RNA sequencing of the skin. Results: The AD skin proteome demonstrated significant upregulation in lesional and even in nonlesional skin compared with controls in inflammatory markers (matrix metalloproteinase 12; T-helper cell [Th]2/interleukin [IL]-1 receptor-like 1[IL1RL1]/IL-33R, IL-13, chemokine [C-C motif] ligand [CCL] 17; Th1/C-X-C motif chemokine 10; Th17/Th22/PI3, CCL20, S100A12), and in cardiovascular-associated proteins (E-selectin, matrix metalloproteinases, platelet growth factor, myeloperoxidase, fatty acid binding protein 4, and vascular endothelial growth factor A; false discovery rate, <0.05). Skin proteins demonstrated much higher and significant upregulations (vs controls) compared with blood, suggesting a skin source for the inflammatory/cardiovascular profile. Gene and protein expressions were correlated (r = 0.410, P <. 001), with commonly upregulated inflammatory and cardiovascular risk-associated products, suggesting protein translation in skin. Limitations: Our analysis was limited to 354 proteins. Conclusions: The AD skin proteome shows an inflammatory and cardiovascular signature even in nonlesional skin, emphasizing the need for proactive treatment. Skin proteomics presents a sensitive option for biomarker monitoring.