High-throughput proteomics identifies inflammatory proteins associated with disease severity and genetic ancestry in patients with hidradenitis suppurativa

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with a greater prevalence and disease burden in patients who identify as African American and those with a family history of HS, suggesting a strong genetic component to its pathogenesis. OBJECTIVES: To evaluate the relationship between plasma inflammatory protein expression, HS disease severity and genetic ancestry in a diverse cohort of patients with HS. METHODS: We performed a case-control, single-centre study of patients with HS and age-, sex- and ethnicity-matched healthy control participants. We profiled circulating inflammatory proteins using Olink® high-throughput proteomics and determined genetic ancestry from whole-genome sequencing data. RESULTS: Using linear regression, we identified novel proteins associated with HS, after adjusting for age, sex and ethnicity. Our analysis also revealed differences in the inflammatory proteome linked to disease severity. Specifically, we found that plasma levels of interleukin (IL)-6 can distinguish between different Hurley stages, indicating that IL-6 may serve as a marker of disease severity. Additionally, we found variations in inflammatory protein levels based on genetic ancestry: patients with predominantly African ancestry exhibited higher levels of inflammatory proteins associated with neutrophilic inflammation, while those with predominantly European ancestry showed increased levels of T helper 1-related inflammatory proteins. CONCLUSIONS: Although we were unable to account for treatment status or comorbidities that may influence the level of inflammatory cytokines, genetic ancestry and disease severity may influence the plasma inflammatory profile in patients with HS.