Dupilumab primarily acts on the IL13 expression of the MSCs in individuals with AD, which can improve the signs and symptoms of the disorder.
Atopic dermatitis (AD) is an inflammatory skin disease, which appears during early childhood in 15–30% of cases, and usually resolves before the onset of puberty. However, more than 50% of the patients experience persistence of AD into adulthood. The prevalence of adult AD has increased in recent decades, particularly in industrialized nations. According to current estimates, the prevalence of AD in children is 10–20%, whereas the prevalence of AD in adults is approximately 2–8%.
AD is characterized by increased transepidermal water loss, improved Langerhans cell antigen presentation, and reduced skin hydration resulting from skin barrier breakdown. The immunologic features include the release of cytokines and the activation of T helper type 22 (Th22) and Th2 cascade. Regarding the pathogenic AD model, the skin-derived mesenchymal stem cells (MSCs) in patients with AD are substantially different from MSCs in individuals without AD. Dupilumab selectively acts on IL4 and IL13 and reduces Th2 response.
This prospective case-control analysis, published in the Journal of Clinical Medicine, evaluated the expression of Th1, Th2, and Th17 in MSCs in patients with AD compared to healthy individuals. The study comprised two groups, the study group and the control group, with 11 participants in each group. Two dermatologists made the diagnosis as per Italian AD guidelines. MSCs from the study subjects were isolated and cultured. The researchers performed immunofluorescence and immunocytochemical analyses on these cells to assess IL4 and IL13. The cytokine levels in the study participants were measured using the commercial ELISA kit.
The findings of this study confirmed the overexpression of IL6 and IL13 in the MSCs derived from participants in the study group with AD compared to the MSCs derived from the participants in the control group. The lesional levels of these cytokines are associated with the severity of AD in adults. The involvement of these cytokines points toward MSCs as the potential molecular therapeutic target for AD. The researchers found the levels of IL4 expression to be variable and of less significance than IL13. This indicates that IL4 is associated with the Th2 response, and the central key player in the dermatological manifestations of AD is IL13. This study also revealed that Dupilumab significantly improves the Eczema Area and Severity Index (EASI) score in study participants with AD, with the major target being IL13.
In summary, this prospective case-control analysis suggested that the primary target of Dupilumab is IL13, which plays a central role in the development of the inflammatory skin disorder, AD. Therapeutic intervention targeting MSCs in AD can alter the course of the disease.
References
Campanati, A., Orciani, M., Marani, A., Di Vincenzo, M., Magi, S., Gregoriou, S., Diotallevi, F., Martina, E., Radi, G., & Offidani, A. (2022). Mesenchymal Stem Cells Profile in Adult Atopic Dermatitis and Effect of IL4-IL13 Inflammatory Pathway Inhibition In Vivo: Prospective Case-Control Study. J Clin Med, 11(16). https://doi.org/10.3390/jcm11164759
