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

Abstract 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. Objective To evaluate the relationship between plasma inflammatory protein expression, HS disease severity, and genetic ancestry in a diverse cohort of patients with Hidradenitis Suppurativa. Methods We performed a case-control study of patients with HS compared to age-, sex-, and ethnicity-matched healthy controls. 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 IL6 levels can distinguish between different Hurley stages, indicating that IL6 may serve as a marker of disease severity. Additionally, we observed 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 Th1-related inflammatory proteins. Limitations Single-center study. Limited sample size. Unable to account for treatment status or comorbidities that may influence the level of inflammatory cytokines. Conclusion Genetic ancestry and disease severity influence the plasma inflammatory profile in patients with HS.