Spatial Transcriptomic Analysis of Early and Late Stages of Hidradenitis Suppurativa

Methods: Skin biopsies from a total of 15 patients with early and late-stage HS were analyzed using spatial transcriptomics, with 6 samples from these patients further analyzed using single-cell RNA sequencing (scRNA-seq). Gene expression profiles were compared to the epidermal epithelium of acne conglobata in spatial transcriptomics and to psoriasis samples in scRNA-seq as controls. Results: Spatial transcriptomics revealed extensive dermal immune activation from the early stage of HS, including a prominent B-cell signature (immunoglobulins, CD19, MS4A1), neutrophilic infiltration (CD177, MPO, ELANE), and robust IL-23/IL-17 axis, with enriched expression of T17-inducing transcripts (TGFB3, RUNX1, BATF) and T17 cytokines (IL17A, IL17F, IL21). ScRNA-seq confirmed marked plasma cell and B-cell expansion in HS and identified potentially multifunctional B-cells expressing pro-inflammatory cytokines (IL7, IL16) in addition to their role in antigen presentation and antibody production. Furthermore, T-cells were identified as the primary producers of the B-cell chemoattractant CXCL13. Conclusions: HS exhibits early and sustained immune activation characterized by B-cell enrichment, IL-23/IL-17 axis activation, and neutrophilic inflammation extending into the deep dermis. These findings highlight the aggressive nature of HS from its onset, suggesting that early therapeutic targeting of the IL-23/IL-17 axis and B-cell-mediated inflammation may prevent disease progression.