Gene Expression Differences Identified in Skin Samples of Mycosis Fungoides, Atopic Dermatitis, and Psoriasis

Background: Recent advances in the understanding of the molecular mechanisms underlying atopic dermatitis (AD) and psoriasis (PSO) have led to the development of multiple targeted therapies. Yet, molecular heterogeneity contributes to inconsistent clinical presentation and therapeutic response. Further, systemic treatment of presumed AD or PSO can lead to delays in both diagnosis and proper treatment of patients with a true diagnosis of mycosis fungoides (MF) – a potentially dangerous clinical mimic of AD and PSO that requires a rigorous histologic and molecular workup to diagnose. Therefore, a non-invasive method to distinguish molecular profiles of MF from AD and PSO could inform accurate diagnoses and avoid inappropriate treatment of MF. We have previously shown transcriptomic differences in AD and PSO samples obtained by a non-invasive scraping technique. However, this technique has not been used to assess differences in gene expression profiles of MF samples. Objectives: To identify gene expression differences based on diagnosis of MF, AD, or PSO and response to targeted systemic AD or PSO therapies. Methods: Lesional baseline samples were assessed from 76 patients (AD, n=24; PSO, n=48; and MF, n=4) enrolled in one of two IRB-approved studies (IDENTITY or SIGNAL-MF). Lesional samples were collected by epidermal scraping and preserved in RNA buffer. Library preparation and next generation RNA sequencing was performed using the Ion AmpliSeq Transcriptome Human Gene Expression panel on the S5 Prime sequencer (ThermoFisher). Clinical responses for AD and PSO were further assessed over 3 months using the eczema and psoriasis area and severity index (EASI and PASI, respectively). Genes were considered differentially expressed if there was a log2fold change >|1.0| and padj <.05. Results: Statistically significant differences in gene expression were observed between AD, PSO, and MF lesions. Further, genes were differentially expressed in baseline skin scrapings obtained from super-responders to dupilumab, which blocks both IL-4 and IL-13 signaling, and PSO therapies including the IL-23 inhibitor risankizumab relative to those who did not achieve ≥90% improvement. Conclusion: A non-invasive molecular test could be developed to distinguish between AD, PSO, and MF, and further identify super-responders to targeted PSO and AD therapies.