Cellular and molecular landscape of early hidradenitis suppurativa lesions reveals early immune microenvironment.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease primarily affecting apocrine gland-bearing areas. Although T helper (Th) 17-mediated inflammation is well-described in advanced HS (Hurley II-III), the immune mechanisms driving early disease remain unclear. To characterize the cellular and molecular environment of early HS lesions and identify potential early drivers of disease, full-thickness skin biopsies from papular inflammatory HS lesions in patients with Hurley stages I-II were analyzed using spatial RNA sequencing and imaging mass cytometry. Distinct immune phenotypes were identified, including B cells, T cells, macrophages, plasma cells, and neutrophils. Early HS lesions showed a marked increase in plasma cells and memory B cells within dermal infiltrates, with high expression of Ig genes and plasma cell markers. T cells aggregated around blood vessels in ectopic lymphoid structures but lacked expression of canonical Th1, Th2, or Th17 cytokines. Early HS is characterized by B-cell activation and plasma cell differentiation, preceding full Th17 pathway activation. These findings highlight B cells and plasma cells as potential early therapeutic targets before the transition to Th17-driven chronic inflammation.