June 3, 2025 — A major new study has identified key skin and blood biomarkers that could help doctors deliver personalized treatment for atopic dermatitis (AD), a common but complex skin condition. Researchers analyzed 951 full-thickness skin samples to understand how gene activity in the skin is linked to disease severity, visible symptoms, and immune responses in the blood.
Atopic dermatitis causes long-term itching and inflammation and varies widely from patient to patient. This variation makes it hard to develop effective treatments for everyone. Using advanced data analysis techniques, researchers discovered specific gene expression patterns—also known as signatures—that match different symptoms and treatment responses.
The study showed that type 2 and type 17 immune responses were strongly linked to major skin symptoms such as redness and thickening. A separate immune response, type 1, was particularly active in a rare form of AD known as lichen amyloidosis. Among patients treated with dupilumab, a widely used therapy for severe AD, those with poor results still showed strong type 17 gene signals in affected skin. Interestingly, even in skin that looked normal, the researchers found increased activity of certain genes, suggesting ongoing immune activity below the surface.
The researchers also identified several genes related to the structure of the skin’s outer layer that were strongly associated with disease severity and response to dupilumab. These findings point to potential biological markers that could help predict which patients will respond to treatment, offering a step forward in personalized care for AD.
The human skin is made up of many types of cells, including keratinocytes, fibroblasts, immune cells, and nerve cells. These work together to protect the body, control immune reactions, and sense the environment. When this balance is disrupted, skin diseases like AD can occur. Although not life-threatening, AD can seriously affect quality of life, with symptoms that appear differently in each person.
So far, studies using blood samples to understand AD have had limited success. Direct skin analysis provides better insight, but traditional skin biopsies are invasive and can cause scarring. To overcome this, the researchers used 1-millimeter punch biopsies, a less invasive technique that still collects deep tissue, including the epidermis and dermis. This allowed them to gather a large number of high-quality samples from both affected and unaffected skin areas.
Because AD symptoms can come and go unpredictably—even during treatment—it is important to understand how the skin’s immune activity changes over time. The study followed some patients over a longer period while they were treated with dupilumab. This helped the researchers track changes in gene activity in response to treatment and during flare-ups.
In total, the study included 1,061 skin samples, of which 1,036 passed quality checks. These came from 156 AD patients, 18 psoriasis patients used for comparison, and 26 healthy individuals. The AD samples included both lesional (affected) and non-lesional (unaffected) skin. Patients had received a range of treatments, including topical steroids and dupilumab. The cross-sectional part of the study included only those who had not taken dupilumab, while the longitudinal analysis followed 24 patients who were treated with it.
RNA sequencing was used to measure gene activity in the samples, with a focus on keratinocytes and fibroblasts. Researchers applied a method called non-negative matrix factorization (NMF) to find both known and previously unrecognized biological pathways involved in AD.
By connecting gene activity to symptoms and treatment outcomes, the study offers new tools for customizing care and monitoring disease progression. While more research is needed, the results represent a step forward in applying precision medicine to atopic dermatitis.
Related Topics:
