The Polygenic Architecture Of Hidradenitis Suppurativa Reveals Signaling Mechanisms That Implicate Epithelial Remodeling

July 2025

Atlas Khan, Poppy A. Gould, Yiming Luo, Errol P. Prens, Lee Wheless, Adriana M. Hung, Theodore G. Drivas, Marylyn D. Ritchie, Amir Hossein Saeidian, Hákon Hákonarson, Michael March, Nick Dand, Juliet N. Barker, Michael H. Simpson, Jake Saklatvala, Xinyi Du-Harpur, Shahir Farnood, Raymond Chung, Charles Curtis, Sang Hyuck Lee, Brian Kirby, Maris Teder- Laving, Külli Kingo, Laurent F. Thomas, Mari Løset, Ben Brumpton, Kristian Hveem, M. Geoffrey Hayes, John Connolly, Frank Mentch, Patrick Sleiman, Kathleen LaRow Brown, Nicholas P. Tatonetti, Olivia D. Perez, Alice Braun, Stephan Ripke, Sadhana Gaddam, Anthony E. Oro, Leah Redmond, Claire A. Higgins, Meng‐Ju Lin, Ernest S. Chiu, Ping Lu, George Hripcsak, Chunhua Weng, Krzysztof Kiryluk, Lam C. Tsoi, Jóhann E. Guðjónsson, Kelsey R. van Straalen, Joshua D. Milner, Lynn Petukhova

hidradenitis suppurativa epithelial remodeling SOX9 CXCR4 CD74 PI3K/AKT signaling pathway NF-κB signaling pathway keratinocyte male pattern hair loss HS male pattern baldness

TLDR Blocking CXCR4 may help treat hidradenitis suppurativa.

The study investigates the genetic basis of hidradenitis suppurativa (HS), an inflammatory skin disease, by conducting a genome-wide association study (GWAS) with 6,300 cases, identifying 12 independent risk loci. The research highlights the role of a gene module involving SOX9, CXCR4, and CD74 in epithelial remodeling and inflammation. Pharmacological inhibition of CXCR4 suggests a regulatory mechanism involving CD74 in PI3K/AKT and NF-κB signaling pathways, affecting keratinocyte behavior. The study also finds a connection between HS and male pattern hair loss, suggesting that CXCR4 blockade could be a potential therapeutic strategy for HS.

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