In-Depth Analysis of the Hidradenitis Suppurativa Serum Proteome Identifies Distinct Inflammatory Subtypes.

Hidradenitis Suppurativa (HS) is a chronic inflammatory dermatosis with presentations ranging from painful nodules and abscesses to draining tunnels. Using an unbiased proteomics approach, we assessed 368 cardiovascular, cardiometabolic and inflammation-related biomarkers in serum of moderate to severe HS patients. HS serum clustered separately from healthy controls and had an up-regulation of neutrophil-related markers (Cathepsin D, IL-17A, CXCL1). Patients with histologically diagnosed dermal tunnels had higher serum Lipocalin-2 (LCN2) levels compared to those without tunnels. Consistent with this, patients with tunnels had a more neutrophilic-rich serum signature, marked by Cathepsin D, IL-17A, IL-17D, and MMP-2 alterations. There was a significant serum-skin correlation between proteins in the serum and the corresponding mRNA levels in skin biopsies, with healthy-appearing perilesional skin demonstrating a significant correlation with neutrophil-related proteins in the serum. Granulocyte-colony stimulating factor (G-CSF, CFS3) mRNA levels in lesional skin significantly correlated with neutrophil-related proteins in the serum, suggesting that CFS3 in the skin may be a driver of neutrophilic inflammation. Clinical parameters significantly correlated with levels of LCN2 and IL-17A in the serum. Using an unbiased, large-scale proteomic approach, we demonstrate that HS is a systemic neutrophilic dermatosis, with a specific molecular signature associated with the presence of dermal tunnels.