Skin transcriptome studies in atopic dermatitis (AD) showed broad dysregulation as well as ‘‘improvement’’ under therapy. These observations were mainly made in trials and based on microarray data.
Objectives: Our aim was to explore the skin transcriptome and the impact of systemic treatment in patients of the TREATgermany registry.
Methods: Biopsy specimens from 59 patients with moderate-to-severe AD before and 30 patients 12 weeks after start of systemic treatment (dupilumab [n 522] or cyclosporine [n 58]) and from 31 healthy controls were subjected to mRNA sequencing. Differential expression, pathway enrichment, correlation, and coexpression network analysis were conducted.
Results: Both lesional and nonlesional skin showed a stable ‘‘core’’ signature characterized by disturbed epidermal differentiation and activation of IL-31/IL-1 signaling. A second dynamic signature showed progressive enrichment for type 2 inflammation, TH17 signaling, and natural killer cell function. Markers correlated with disease activity have functions in epidermal barrier properties and immune modulation. IL4RA was among the top 3 central dysregulated genes. Cyclosporine led to a more pronounced global
transcriptome reversion and normalized TH17 cell/IL23 signaling, whereas dupilumab led to a stronger increase in level of epidermal differentiation markers. Both treatments strongly decreased levels of type 2 markers, but overall the residual profile was still profoundly different from that of healthy skin. Lower levels of IL4RA and IL13 and high IL36A expression were related to a stronger clinical response to dupilumab.
Conclusion: The AD core signature is characterized by dysregulation of genes related to keratinocyte differentiation and itch signaling. A dynamic signature reflects progressive immune responses dominated by type 2 cytokines with an additional role of TH17 and natural killer cell signaling.

O artigo explora o transcriptoma da pele e o impacto do tratamento sistêmico da Dermatite Atópica em pacientes do registro TREAT da Alemanha.


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