Citations 1
Targeting IL-1 controls refractory pityriasis rubra pilaris
Schmauch, Eloi , Severin, Yannik , Xing, Xianying , Mangold, Aaron R. , Conrad, Curdin , Johannsen, Pål, Kahlenberg, J. Michelle , Mellett, Mark , Navarini, Alexander A. , Nobbe, Stefan , Nilsson, Jakob , Linna-Kuosmanen, Suvi , Snijder, Berend , Contassot, Emmanuel , Kolios, Antonios G.A. , Mangold, A R , Johansen, Pål , Navarini, Alexander , Sarkar, Mrinal K , Satyam, Abhigyan , Tsoi, Lam C , French, Lars E , Nilsson, Jakob , Linna-Kuosmanen, Suvi , Kaikkonen, Minna U , Snijder, Berend , Kellis, Manolis , Gudjonsson, Johann E , Tsokos, George C. , Contassot, Emmanuel , Kolios, Antonios G A , Kahlenberg, J Michelle , Sarkar, Mrinal K. , Tsoi, Lam C.
Science Advances | July 3, 2024 | Volume: 10 | Issue: 27 | Pages: No page available
Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease with a poorly understood pathogenesis. Through a molecularly driven precision medicine approach and an extensive mechanistic pathway analysis in PRP skin samples, compared to psoriasis, atopic dermatitis, healed PRP, and healthy controls, we identified IL-1β as a key mediator, orchestrating an NF-κB–mediated IL-1β–CCL20 axis, including activation of CARD14 and NOD2. Treatment of three patients with the IL-1 antagonists anakinra and canakinumab resulted in rapid clinical improvement and reversal of the PRP-associated molecular signature with a 50% improvement in skin lesions after 2 to 3 weeks. This transcriptional signature was consistent with in vitro stimulation of keratinocytes with IL-1β. With the central role of IL-1β underscoring its potential as a therapeutic target, our findings propose a redefinition of PRP as an autoinflammatory keratinization disorder. Further clinical trials are needed to validate the efficacy of IL-1β antagonists in PRP.