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.

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 1-4% 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.

ESDR048 - The transcriptional landscape of hidradenitis suppurativa at single-cell and spatial resolution

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.