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News

Article

Advancements in Molecular Profiling: Differentiating Skin Diseases Through Non-Invasive Techniques

Investigators revealed the development of a non-invasive molecular test utilizing gene expression differences in skin diseases such as atopic dermatitis, psoriasis, and mycosis fungoides, with the potential to accurately diagnose and identify super-responders to targeted systemic therapies.

The 2024 Masterclasses in Dermatology conference in Puerto Rico showcased research in the molecular understanding of common skin diseases, specifically atopic dermatitis (AD), psoriasis (PSO), and mycosis fungoides (MF). This poster presentation highlighted the development of targeted systemic drugs and emphasized the importance of personalized molecular profiles for effective treatment strategies. The challenge of inconsistent clinical presentation and therapeutic response due to molecular heterogeneity was addressed, raising the need for precise diagnostics. The study aimed to distinguish gene expression differences in lesional samples obtained through non-invasive skin scraping techniques, offering insights into accurate diagnoses and tailored therapies.1

Studio Romantic/Adobe Stock

Studio Romantic/Adobe Stock

Methods

The research involved 76 patients enrolled in IRB-approved studies (IDENTITY or SIGNAL-MF), with samples categorized as AD (n=24), PSO (n=48), and MF (n=4). Lesional baseline samples were obtained by gently scraping the skin using a curette, preserving them in a proprietary buffer. The Ion AmpliSeq Transcriptome Human Gene Expression panel on the S5 Prime sequencer was employed for library preparation and next-generation RNA sequencing. Clinical response to targeted systemic therapies, such as dupilumab (Dupixent) for AD and risankizumab(Skyrizi) for PSO, was assessed over 3 months using the eczema area and severity index (EASI) or psoriasis area or severity index (PASI), respectively. The study excluded specific samples to ensureaccurate diagnostic gene expression analysis.

Results

The study revealed robust gene expression obtained from lesional PSO, AD, and MF samples collected through non-invasive skin scraping. Gene expression differences were observed between PSO, AD, and MF lesions, providing a molecular basis for distinguishing these conditions. Notably, AD lesions from super-responders to dupilumab exhibited distinct gene expression patterns, as did PSO lesions from super-responders to risankizumab. These findings suggest a potential correlation between specific gene expression profiles and treatment responsiveness.

Conclusions

The presented research holds significant implications for dermatology practice. The ability to obtain robust gene expression profiles from non-invasive skin scraping offers a promising avenue for accurate and early diagnoses of AD, PSO, and MF. The observed distinctions in gene expression among super-responders to targeted systemic therapies provide valuable insights for tailoring treatment plans. The ultimate goal is to develop a non-invasive molecular test capable of distinguishing between AD, PSO, and MF, as well as identifying super-responders to AD and PSO therapies.

This groundbreaking work aligns with the broader, globaltrend in medicine toward personalized and precision approaches. As technology continues to advance, the integration of molecular profiling into routine dermatological practice could revolutionize the diagnosis and treatment of skin diseases, enhancing patient outcomes and quality of care.2

References

  1. Farberg A, Goldberg M, Quick A, et al. Gene Expression Differences Identified in Skin Samples of Mycosis Fungoides, Atopic Dermatitis, and Psoriasis. Poster presented at: Masterclasses in Dermatology February 16-19, 2024; Puerto Rico.
  2. Manzari MT, Shamay Y, Kiguchi H, Rosen N, Scaltriti M, Heller DA. Targeted drug delivery strategies for precision medicines. Nat Rev Mater. 2021;6(4):351-370. doi:10.1038/s41578-020-00269-6
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