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Targeting of Th17-related cytokines in patients with Darier Disease

Ettinger, M.; Burner, T.; Pospischil, I.; Traxler, J.; Wahl, G.; Altrichter, S.; Lackner, A.; Gratz, I. K.; Kimeswenger, S.; Guenova, E.; Hoetzenecker, W.

2023-01-17 dermatology
10.1101/2023.01.12.22283857 medRxiv
Show abstract

Darier disease (DD) is a rare, inherited multi-organ disorder associated with mutations in the ATP2A2 gene. DD patients often have skin involvement characterized by malodorous, inflamed skin and recurrent, severe infections. Therapeutic options are limited and inadequate for the long-term management of this chronic disease. Using gene and protein expression profiling assays, we demonstrate enhanced expression of Th-17-related genes and cytokines and increased numbers of Th17 cells in six DD patients. We prove that targeting the IL-23/-17 axis in DD with monoclonal antibodies is an effective and safe therapy for DD patients, leading to significant clinical improvement. As DD is a chronic, relapsing disease, our findings provide new options for the long-term management of skin inflammation in patients with DD.

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