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 Th17-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 early papulonodular HS lesions (Hurley Stage I–II) were analyzed using spatial RNA sequencing and Imaging Mass Cytometry (IMC).
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 immunoglobulin 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.