Longitudinal skin tape strip global proteomic assessment reveals normalization of epidermal development in atopic dermatitis patients treated with dupilumab

Atopic dermatitis (AD) is characterized by epidermal dysfunction and interleukin (IL)-4/IL-13-predominant inflammation. Dupilumab, a monoclonal antibody that targets IL-4Rα, has demonstrated clinical efficacy/safety in AD. The skin barrier proteomic changes in AD patients with dupilumab treatment are not established. Longitudinal lesional and non-lesional skin tape stripping (STS) was performed for 20 healthy volunteers and 20 AD patients treated with dupilumab for 16 weeks. STS protein extracts were examined by liquid chromatography tandem mass spectrometry. Skin proteomic profiles were correlated with AD clinical parameters (SCORAD, EASI) and transepidermal water loss (TEWL AUC10). 490 proteins were detected in ≥80% of AD and healthy STS. 139 proteins were differentially expressed between AD and healthy individuals, 90 of which were significantly increased (cluster 1) (p<0.0001) and 49 were significantly reduced (cluster 2) (p<0.0001) in AD as compared to healthy skin in unsupervised cluster analysis at baseline. Functionally, cluster 1 proteins were enriched for markers of epidermal hyperplasia—intermediate keratin filaments (KRT6, KRT16, KRT17, KRT14, KRT5, DSP), glycolytic proteins (PKM, ALDOA, LDHA), proteins involved in actin filament organization (ACTB, ACT, TPM2), and protein translation (ribosomal subunits). Expression of these proteins significantly decreased in AD lesional skin with dupilumab treatment (p=0.0001) and approached levels seen in healthy skin at week 16. The decrease in expression of cluster 1 proteins in response to treatment significantly correlated with TEWL AUC10 decrease in AD lesional skin (r=0.73, p<0.001). Longitudinal proteomic assessment of dupilumab-treated AD skin established significant inhibition of epidermal hyperplasia markers, which correlated with significant improvements in TEWL.