practicaldermatology.com
Gene expression abnormalities not only reflect the severity of psoriatic lesions but also predict treatment response, according to a recent study published in JID Innovations.
Researchers on the study analyzed gene expression profiles in psoriatic skin using Gene Set Variation Analysis (GSVA) and other advanced methodologies. They also developed a gene expression-based score (PsoriaCIS) that they said "that serves as a molecular readout of disease severity and treatment efficacy."
Psoriatic lesions exhibit significant disruptions in gene expression, and the analysis revealed signatures for neutrophils, keratinocytes, and inflammatory cytokines, including IFN, IL-12, IL-1, and TNF. Treatment with various therapeutic agents resulted in a reduction of abnormalities, normalizing gene expression to levels observed in nonlesional skin. Baseline gene expression patterns were linked to treatment responsiveness, with specific abnormalities correlating with clinical improvement in responders. Nonresponders showed smaller changes in gene expression over time. The study’s transcriptomic scoring system demonstrated a positive correlation with Psoriasis Area and Severity Index (PASI) scores in clinical responders.
"We have developed PsoriaCIS as a molecular tool to assess the degree of immune pathology in patients with psoriasis and demonstrated the ability of PsoriaCIS to convey changes to the molecular profiles of patients with effective therapy," the authors wrote. "However, because this initial implementation of PsoriaCIS was generated using currently available datasets, as with any biomarker, additional prospective studies are needed before it can be used to support the treatment of psoriasis."
They were optimistic, however, that tool could be built upon to eventually bolster the use of PsoriaCIS as an additional tool for enhancing the impact of care.
"Despite these limitations, the results of this study provide a comprehensive analysis of psoriasis treatment effects on gene expression and offers numerous potential avenues, including a molecular scoring system, for improving the management of patients with psoriasis," they wrote. "As a clinical biomarker, PsoriaCIS has the potential to support clinical care of psoriasis by aiding in the selection of the most effective therapeutic agent for each individual and to monitor the effects of treatment over time. Thus, by incorporating additional studies and therapeutic agents, PsoriaCIS could be used alongside current methodologies to ensure that each patient is given the optimal treatment regimen over time."
Source: Shotri S, et al. Journal of Investigative Dermatology Innovations. 2025. Doi:10.1016/j.xjidi.2024.100333