048 the Transcriptional Landscape of Hidradenitis Suppurativa at Single-Cell and Spatial Resolution

Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis characterised by painful nodules, abscesses and sinus tracts, typically in flexural sites. It has an estimated prevalence of 2% and can be severely debilitating. The inflammatory and immune landscape underlying HS remains poorly understood and treatment options are limited or only partially effective. We have performed global transcriptional profiling at single-cell and spatial resolution on axillary HS skin. This has revealed striking differences in comparison to healthy skin and other inflammatory skin diseases such as psoriasis and eczema. We find over-representation of plasma cells in the immune infiltrate in comparison with healthy and other inflammatory skin diseases. Transcriptional profiling of the B cell population suggests that in HS tissue there is a subtype of cells with an ‘activated memory’ profile, which have been described in autoimmune diseases. The presence of this B cell population, which express markers associated with class switch recombination, supports the concept of diseased skin as having the potential of acting as tertiary lymphoid tissue. There is also expansion of a fibroblasts subpopulation associated with inflammation and vascular endothelial cells, and the follicular units show a range of transcriptional profiles; ranging from a profile similar to normal follicular epithelial cells to that of the interfollicular epidermis in hyperkeratinised states. Modelling of the cell-cell interactions and subsequent pathway analysis suggests that immune cells drive the transition to this IFE-like profile. My findings support the paradigm of HS as an autoinflammatory keratinisation disorder. It also supports the idea of investigating the repurposing of drugs that have been developed for other autoimmune or autoinflammatory diseases with similar underlying immune cell profiles.