Neutrophil Extracellular Traps Are Widely Distributed Across Lesional and Perilesional Hidradenitis Suppurativa Skin, and Elevated Serum NET Markers Associate With Moderate to Severe HS Disease

Neutrophils are scarce in healthy skin but infiltrate lesions of hidradenitis suppurativa (HS) patients. Activated neutrophils release proinflammatory neutrophil extracellular traps (NETs), which have been implicated in the pathophysiology of HS. This study aimed to describe the distribution of NETs relative to the features of HS skin lesions and reveal whether serum NET markers were elevated in association with disease activity. Immunohistochemistry assessed the distribution of the key NET component citrullinated histone H3 (CitH3) in lesional, perilesional, and unaffected HS skin. Several markers of NETs (nucleosomes, calprotectin, and CitH3) were quantified in HS serum with ELISA. HS lesional skin biopsies showed increased CitH3-positive staining compared to unaffected skin. This signal was widely distributed across both lesional and perilesional regions of HS skin and was associated with HS structures such as the lining of epithelialized skin tunnels. Moreover, several NET-associated markers were elevated in the serum of HS patients compared to healthy volunteers and correlated with each other. Finally, serum NET markers showed significant elevation in patients with moderate to severe disease activity based on IHS-4 scores, compared to those with no or mild activity. Elevated NET markers are widely distributed in HS skin and serum. These data indicate that NET-associated markers in serum are candidate biomarkers for HS disease severity. The results confirm the rationale for anti-inflammatory therapy targeting NETs in HS.