Researchers Uncover Clues Driving PsO Spread and Severity

NYU Langone's Dr. Shruti Naik discusses the new findings with DermWire.

New research sheds light on the cellular changes that drive psoriasis severity and also offers important clues about how the disease spreads to other parts of the body. 

Specifically, the location of clusters of fibroblasts and macrophages tend to occur more commonly in the upper layers of the skin in more severe cases of psoriasis. In addition, gene activity and signatures increased in more than three dozen molecular pathways tied to metabolism and control of lipid levels, and this increased gene activity even occurred in clear skin in skin samples from patients with moderate-to-severe psoriatic disease.

Researchers used spatial transcriptomics to chart these molecular and cellular interactions occurring in intact skin samples from 11 men and women with mild to severe cases of psoriatic disease, plus three healthy adults without psoriasis. This novel technology creates a broad image-based map of where cells are located in tissues and highlights the other cells that they are communicating with.

Study author Shruti Naik, PhD, an assistant professor in the Departments of Pathology and Medicine at the Ronald O. Perelman Department of Dermatology at NYU Langone in New York City, spoke with DermWire about the new findings and their implications.

DermWire: What did we learn from this study?

Shruti Naik, PhD: “The study advances our understanding of the molecular signatures of psoriatic disease, particularly in uninvolved skin. While distal skin looks healthy and asymptomatic, there are changes that are occurring that may have significant consequences for comorbidities on a molecular level. We need to look at the patients as a whole and think ‘How do we go from localized lesion to cardiovascular disease, a comorbidity of psoriasis, or from local inflammation to whole body inflammation’?  We are just starting to consider that changes in uninvolved skin could be contributing to larger changes that result in metabolic disturbances. We think about things we can see or feel, but there are subtle small changes that happen throughout the body and may not be at the site of disease that have profound consequences. Now, with spatial transcriptomics, we can visualize these changes in tissues with more than just pathology.”

DermWire: Will this insight and technology bring us closer to personalized medicine in psoriasis?

Dr. Naik: “Yes. In the coming years, we may be able to diagnose a patient and say that these are all of the changes in genes and cells and this is what we need to tackle in this patient versus that patient. That’s the direction we are going in. Further research is also planned in larger groups of patients and in lesioned and non-lesioned skin from the same patients to determine how disease clears on its own in some and why patients respond differently to the same anti-inflammatory medications.”

The study is published online in Science Immunology on June 2, 2023.