824 Spatial transcriptomic analysis of HS skin lesions reveals that tunnels are immunologically active and activity correlates with disease severity

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by neutrophil-rich nodules, abscesses or tunnels (sinus tracts). Tunnels, unique to HS, are deep dermal cavities lined with squamous epithelium that immunologically active, contributing pathology. The role of in driving ongoing poorly understood. We used the GeoMX Digital Spatial Profiler analyze a moderate (Hurley stage II) compared severe III) HS lesion explore biological differences between and within lesions. Four distinct regions per sample were analyzed: tunnel epithelium, immune infiltrate adjacent tunnel, not associated sub-epidermis. observed higher expression keratinization genes (e.g. K16, S100A7) more differentiated tunnel. Genes for proinflammatory cytokines IL36, IL1B), chemokines CXCL1, CCL20), neutrophil activation ELANE, MPO) B cells (CD79A, SDC1) had lesion. found spatial gradient gene IL36 neutrophil-attracting (CXCL1, CXCL8), from high lower Both lesions displayed these gradients, but those pronounced. Conversely, gradients fibroblast-related PDGFR, FAP) sub-epidermis epithelium. These data suggest marked increase inflammation cytokine chemokine support idea potentially disease, rather than representing remnants prior disease.