Targeting IL-1 controls refractory Pityriasis rubra pilaris

• DOI: 10.21203/rs.3.rs-3433295/v1
• Publication Date: 2023-10-13T22:08:11Z
• Authors: Eloi Schmauch; Yannik Severin; Xianying Xing; Aaron Mangold; Curdin Conrad; Pål Johannsen; Michelle Kahlenberg; Mark Mellett; Alexander Navarini; Stefan Nobbe; Mrinal K. Sarkar; Abhigyan Satyam; Lam C. Tsoi; Lars E. French; Suvi Linna-Kuosmanen; Minna U Kaikkonen; Berend Snijder; Manolis Kellis; Johann E. Gudjonsson; George C. Tsokos; Emmanuel Contassot; Antonios G. A. Ko...

Abstract Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease which lacks efficacious standard-of-care treatments. Molecular studies of skin lesions revealed that IL-1β is central to the pathogenesis of PRP. Treatment of three patients with the IL-1-targeting biologics anakinra and canakinumab resulted in rapid clinical improvement and reversal of the PRP-associated molecular signature. We identified an NF-κB-mediated IL-1β-CCL20 axis central to the inflammatory response in PRP. Our results reveal the central role of IL-1β signaling in the pathogenesis of PRP and highlights its prominence as a therapeutic target.