Kristijan Pažur*,1, Wojciech
Francuzik*,1, Hanin El-Mahmoud1,
Magdalena Kraft2, and Margitta
Worm1,✉
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