Kristijan Pažur^*,1, Wojciech Francuzik^*,1, Hanin El-Mahmoud¹, Magdalena Kraft², and Margitta Worm^1,✉

30. 05. 2023

Background: Identification of biomarkers is required for a systems medicine approach and personalized treatment in AD. These biomarkers may not only aid in diagnosing but also might be suitable to predict the effectiveness of targeted treatment.

Objective: We aimed to identify proteomic, microbial, and miRNA biomarkers in atopic dermatitis patients and investigated their course in relation to the clinical response upon anti-IL-4Rα therapy.

Methods: Proteomic and miRNA screening was performed in AD patients in comparison to healthy controls. Differentially regulated serum proteins, miRNA, and selected skin microbiota were measured consecutively in 50 AD patients before and upon systemic dupilumab treatment. A random forest classifier was used to predict the outcome of dupilumab therapy based on the initial biomarker patterns.

Results: We identified 27 proteomic candidates, miRNA, and 3 microbial strains to be dysregulated in AD. Besides the well-known chemokine CCL17 other proteins i.e., CCL13, CCL22, E-selectin and BDNF were differently regulated and significantly associated with treatment response. By contrast neither the microbial changes nor the miRNA pattern were found to be associated with treatment response upon dupilumab treatment.

Conclusion: AD patients display defined dysregulations regarding their systemic proteomic serum profile, miRNA patterns, and their skin microbiome. The proteomic profile and selekted skin bacteria changed profoundly upon anti-IL-4Rα therapy which was associated with an overall clinical response. This was not seen in miRNA-related biomarkers. Our findings support the hypothesis that biomarker profiles reflect treatment responses and may in the future be used to develop a personalized medicine approach for the treatment of atopic dermatitis patients.

^* These authors contributed equally to this work.

¹ Department of Dermatology, Venereology and Allergology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.² Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

^✉ Correspondence: Margitta Worm <margitta.worm@charite.de>, Division of Allergy and Immunology, Department of Dermatology, Venereology and Allergology, Charitéplatz 1, 10117 Berlin, Germany, +49 30 450 518092

Capsule summary: Serum biomarker profiles and skin microbial colonization patterns correlate well with established clinical severity scores. Baseline CCL17, E-selectin, Notch 1 and CD25s levels may indicate if patients will respond well to dupilumab therapy, however further validation is required.

Keywords: atopic dermatitis; biomarkers; dupilumab; miRNA; microbiome