P88 Spatial transcriptomic profiling reveals body site-specific inflammatory differences in psoriasis lesions

Abstract Psoriasis is a common chronic inflammatory skin disease. A variety of treatment options lead to substantial improvement of most psoriasis plaques; however, recurrence of psoriasis in previously affected areas is common. Additionally, it can be challenging to reach disease resolution in certain hard-to-treat areas such as scalp and lower extremity (LE). Here, we map histologic and spatial transcriptomic differences between psoriasis lesions across different anatomical locations, to understand if differences in the inflammatory profile can be linked to plaque-site-specific treatment resistance. Quantitative immunohistochemical analysis and transcriptomic digital spatial profiling were performed on skin punch biopsies obtained from unaffected areas on the trunk, lesional areas of the scalp, upper extremity, and LE of 12 patients with psoriasis. Histological analysis showed no significant differences in epidermal thickness among lesional (LS) skin from different body locations. Immunohistochemical markers (CD3, CD4, CD8, CD103, CD207, RORγt, FOXP3 and MPO) were higher in LS skin compared with non-lesional (NL) skin but did not differ significantly between LS sites. Whole transcriptome spatial RNA profiling identified several differentially expressed genes that distinguished LS from NL skin and revealed site-specific transcriptomic differences. Notably, IL-23 signalling was significantly enriched in the LE epidermis, and IL-17 signalling was more pronounced in the epidermis of LS samples. These findings highlight minimal histological and immunohistochemical variation, yet significant transcriptomic and pathway differences between psoriasis body locations, suggesting potential future targets for site-specific therapeutic strategies.