New Findings in Hidradenitis Suppurativa Pathophysiology: Focus on B Cells, BAFF, BTK, and SYK

Abstract Purpose of Review This review examines recent advances in the understanding of the immunopathogenesis of hidradenitis suppurativa (HS), with a particular emphasis on the emerging roles of B cells, plasma cells, tertiary lymphoid structures (TLSs), and the BAFF-BTK-SYK axis. It also explores the therapeutic implications of these findings and the potential for immune-targeted interventions. Recent Findings Recent studies employing spatial transcriptomics, single-cell RNA sequencing, and proteomics have redefined HS as a disorder of significant humoral immune dysregulation. B cells and plasma cells are predominant in lesional skin, particularly in Hurley stage 3 disease, where they contribute to TLS formation, local autoantibody production, and chronic inflammation. Neutrophils also perpetuate disease through the release of BAFF and NETs, driving plasma cell survival and autoimmunity. Targeted therapies inhibiting BAFF (e.g. ianalumab), BTK (e.g. remibrutinib) and SYK (e.g. fostamatinib) show early promise. Summary The pathogenesis of HS extends beyond innate immune dysregulation to include key components of the adaptive and humoral immune response. B cells, plasma cells, and TLSs play pathogenic roles in a subset of patients, offering new avenues for targeted therapy. Immune endotyping and biomarker stratification may enhance the efficacy of emerging BAFF-, BTK-, and SYK-targeted therapies, ushering a new era of personalised treatment for HS.