The role of lipocalin-2 in the pathophysiology of hidradenitis suppurativa.

Lipocalin-2 (LCN-2) is a multifunctional glycoprotein that is weakly expressed in the skin and serum in healthy individuals, but it is associated with a range of inflammatory, metabolic, and cardiovascular conditions. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent nodules, abscesses, and tunnels in skin folds, which reflect neutrophilic infiltration and inflammation in the deep portion of the dermis. Recent studies have shown elevated LCN-2 levels in several skin diseases, including psoriasis, atopic dermatitis, skin wounds, keratoacanthoma, and squamous cell carcinoma. Its role as a potential biomarker is being investigated in over 70 trials. Research data consistently show LCN-2 is one of the most significantly elevated biomarkers in the serum and skin samples of patients with HS compared with healthy controls. Given the role of LCN-2 as a downstream gene in the T helper 17 (Th-17) pathway, Th-17 inflammation plays a central role in the pathogenesis of HS. Exposing granulocytes and keratinocytes to LCN-2 in vitro also leads to the oversecretion of proinflammatory cytokines and chemokines. Neutralizing LCN-2 as a potential treatment target could reduce inflammatory cell infiltration into the deep part of the dermis. It might also suppress the Th-17 immune response. The role of LCN-2 as a biomarker for disease activity may even differentiate LCN-2 as a unique HS classifier, and prospective clinical studies may provide validation.