Elena Goleva PhD , Evgeny Berdyshev PhD , Simion Kreimer PhD , Julie A. Reisz PhD , Angelo D’Alessandro PhD , Irina Bronova PhD , Taras Lyubchenko PhD , Brittany N. Richers BS , Clifton F. Hall MS , Olivia Xiao BS , Anna-Sofia Bronoff BS , Shantanu Bafna MS , Inoncent Agueusop PhD , Emilie Gloaguen PhD , Joseph Zahn MD , Robert Bissonnette MD , Annie Zhang MD , Donald Y.M. Leung MD, PhD
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引用次数: 0
Abstract
Background
Inhibition of IL-4/IL-13–driven inflammation by dupilumab has shown significant clinical benefits in treatment of atopic dermatitis (AD).
Objective
Our aim was to assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment.
Methods
Skin tape strips (STSs) were collected from lesional/nonlesional skin of 20 patients with AD during a 16-week dupilumab treatment course and from 20 healthy volunteers (HVs) followed for 16 weeks. STS extracts were examined by liquid chromatography–mass spectrometry proteomic analysis and targeted metabolomics.
Results
Approximately 2500 individual proteins were identified in the STS extracts. Of those proteins, 490 were present in at least 80% of the AD and HV skin samples and differentially expressed in the AD skin; the levels of 249 proteins were significantly reduced (cluster 1), and the levels of 136 were significantly increased (cluster 2) in the AD skin versus in the HV skin (both P < .0001). Functionally, cluster 1 included proteins involved in epidermal barrier formation, lysosomal enzymes required for lamellae assembly, and oxidative response. Cluster 2 was enriched for markers of epidermal hyperplasia, glycolytic enzymes, and actin filament proteins. A significant increase in cluster 1 and a significant inhibition of cluster 2 proteins expression were achieved in AD skin by 16 weeks of dupilumab treatment (P < .0001 for both vs baseline), approaching the levels in HV skin. These improvements were also revealed in differential metabolite changes in the STS extracts, including amino acids, nucleotide breakdown products, and antioxidants.
Conclusion
Longitudinal integrated assessment of the skin proteome and metabolome in patients with AD who were treated with dupilumab established significant inhibition of epidermal hyperplasia and improvement in epidermal differentiation. The identified changes were linked to improvements in clinical AD skin assessments, including improvements in transepidermal water loss and disease severity.
期刊介绍：
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.
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