Proteomics identifies blood biomarkers associated with disease severity and genetic ancestry in hidradenitis suppurativa

Summary: Abstract Body: Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition that disproportionately affects individuals of African ancestry and those with a family history, suggesting a genetic basis for the disease. Despite its burden, no clinically validated biomarkers exist to guide treatment or predict outcomes. Previous biomarker studies have been limited by small sample sizes, impeding control for demographic factors such as age, sex, and ethnicity. Identifying robust biomarkers is essential to improve disease management and prognosis. This case-control study employed high-throughput proteomics and whole-genome sequencing (WGS) to address these gaps. Circulating inflammatory proteins were analyzed using Olink high-throughput proteomics in 72 HS patients and 24 age-, sex-, and ethnicity-matched healthy controls (HCs). Genetic ancestry was determined through WGS, and linear regression was used to adjust for demographic variables and identify significant biomarkers. A total of 55 novel inflammatory biomarkers were identified in HS patients compared to HCs, 32 of which were previously unreported. Among these, 26 proteins correlated with disease severity, with IL-6 and MMP1 levels distinguishing between Hurley stages. Genetic ancestry significantly influenced inflammatory profiles: African ancestry was associated with elevated neutrophilic inflammation markers, while European ancestry correlated with increased Th1-related proteins. These findings underscore the interplay between disease severity, genetic ancestry, and inflammatory profiles in HS, paving the way for biomarker-driven, personalized treatment strategies. Peter Dimitrion¹, Rachel Krevh¹, Jesse Veenstra^{1, 2}, Iltefat Hamzavi¹, Indra Adrianto^{1, 2}, Li Zhou^{1, 2}, Qing-Sheng Mi^{1, 2} 1. Dermatology, Henry Ford Health System, Detroit, MI, United States. 2. Henry Ford Health + Michigan State University Health Sciences, Detroit, MI, United States. Minoritized Populations and Health Disparities Research