Blood transcriptome profiling identifies 2 candidate endotypes of atopic dermatitis

Area of Science:

• Immunology
• Genomics
• Dermatology

Background:

• Limited research exists on blood transcriptome analysis in atopic dermatitis (AD).
• Understanding molecular signatures in AD is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate blood transcriptomic features in adults with moderate to severe atopic dermatitis.
• To identify distinct molecular endotypes within AD patients.

Main Methods:

• Blood messenger RNA sequencing was performed on 60 adults from the TREATgermany registry, including patients before and after dupilumab treatment, and an independent cohort.
• Analysis included patient clustering, differential gene expression, correlation and coexpression network analysis, and unsupervised learning.

Main Results:

• Atopic dermatitis patients exhibited distinct inflammatory expression signatures, segregating into two clusters based on eosinophil signaling.
• The eosinophil-high endotype showed greater transcriptomic dysregulation and correlation with disease activity, while the eosinophil-low endotype had minimal dysregulation.
• Dupilumab treatment modulated immune responses, decreasing innate immunity and increasing lymphocyte signatures; super responders were more frequent in the eosinophil-low endotype.

Conclusions:

• Atopic dermatitis can be stratified into eosinophilic and noneosinophilic endotypes.
• This endotype stratification may inform the design of clinical trials and personalized treatment strategies for AD.