Spatial transcriptomic profiling reveals novel insights into psoriasis pathogenesis

Key takeaways:

• Lesional and distal, nonlesional areas stratified by disease severity and not by the presence of systemic disease.
• Severe psoriasis may alter the cellular and metabolic makeup of unaffected skin.

Spatial transcriptomic profiling showed that lesional and distal, nonlesional areas in patients with psoriasis stratify by disease severity and not by the presence of disease, according to a study from NYU Langone Health.

“Psoriasis is a devastating and complex disease with many factors contributing to inflammation. This disease often has many other comorbidities including arthritis and cardiovascular disease,” Shruti Naik, PhD, co-senior investigator and assistant professor in the departments of pathology, medicine and the Ronald O. Perelman department of dermatology at NYU Langone Health, told Healio. “Currently we have powerful treatments that control skin symptoms but not a very good understanding of how the disease evolves from skin to other areas of the body. Our study provides new clues that molecular changes in uninvolved skin may contribute to these processes.”

Using novel, spatial transcriptomic profiling, Naik and colleagues analyzed 25 healthy skin biopsies from three healthy controls and 11 patients with human psoriasis (PsO) and psoriatic arthritis (PsA). Results showed that there are major differences in immune microniches between healthy and inflamed skin.

Shruti Naik

Core disease features were identified in all active lesions by tissue scale-cartography which showed the emergence of an inflamed suprabasal epidermal state and traces of B lymphocytes.

Notably, the authors found that the lesional and distal nonlesional samples stratified by skin disease severity and not by systemic disease presence. This may be due to the presence of macrophage, fibroblast and lymphatic enrichments in spatial regions that contained gene signatures linked to metabolic disfunction, the authors wrote.

Nevertheless, this finding indicates severe PsO may not only affect lesional skin but may also alter the cellular and metabolic structure of distal, unaffected skin regions, according to the study.

“Taking a wholistic approach and examining not just the skin plaque but other skin areas, as we have done, has revealed changes that could have tremendous effect on disease severity and progress,” Naik told Healio.