1323 Human dermal fibroblasts and mast cell populations are altered in hidradenitis suppurativa, with epithelial-mesenchymal-transition signals ameliorated by spleen tyrosine kinase antagonism.

Hidradenitis Suppurativa is a chronic inflammatory disease, the pathogenesis of which incompletely understood. Fibroblasts and Mast cells are important mediators wound healing fibrosis, disturbed in HS tissue. We demonstrate aberration fibroblast mast cell populations whole tissue RNA seq analysed by CIBERSORTx in-silico deconvolution, validated Nanostring Gene Expression Immunohistochemistry. Populations SFRP2+ fibroblasts activated expanded lesional tissue, with specific increases associated epithelialised tunnels epidermal “budding”. Reduction SFRP1+ were seen no change CXCL12+ population. Markers Epithelial Mesenchymal Transition including SNAI2, ZEB2, TWIST1 N-Cadherin upregulated compared to normal site-matched controls, greater expression nodules. Treatment oral Spleen Tyrosine Kinase Inhibitor Fostamatinib 100mg BID for 4 weeks as part an open label proof concept clinical trial (NCT05040698) demonstrated significant alterations fibroinflammatory genes IL13, TPSAB1/B2, SNAI2 HSP90AA1.Significantly altered pathways pertaining inflammation, proliferation production immunoglobulins also identified. This study presents novel data regarding heterogeneity association fibroblasts, epithelial mesenchymal transition potential reversibility use antagonism.