The proteomic skin profile of moderate-to-severe atopic dermatitis patients shows an inflammatory signature
Journal of the American Academy of Dermatology, 2019
Pavel A., Zhou L., Diaz A., Ungar B., Dan J., He H., Estrada Y., Xu H., Fernandes M., Renert-Yuval Y., Krueger J., Guttman-Yassky E.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Dermatological Diseases | Pathophysiology Patient Stratification | Serum Tissue Lysate |  Olink Target 96 |
Abstract
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 utilizing 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 non-lesional biopsies and blood from moderate-to-severe AD (n=20) and healthy (n=28) individuals using OLINK proteomics (utilizing 10μg/10μL for skin and blood) and RNAseq (skin).
Results: The AD skin proteome demonstrated significant upregulation in lesional and even in non-lesional skin compared to controls in inflammatory markers (MMP12; Th2/IL1RL1/IL-33R, IL-13, CCL17; Th1/ CXCL10; Th17/Th22/PI3, CCL20, S100A12), and in cardiovascular-associated proteins (SELE, MMPs, PGF, MPO, FABP4, VEGFA; FDR<0.05). Skin proteins demonstrated much higher and significant upregulations (vs. controls) compared to blood, suggesting a skin source for the inflammatory/cardiovascular profile. Gene and protein expressions were correlated (r=0.410, P<0.001), with commonly upregulated inflammatory and cardiovascular-risk 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 non-lesional skin, emphasizing the need for proactive treatment. Skin proteomics presents a sensitive option for biomarker monitoring.