Targeting of Th17-related cytokines in patients with Darier Disease

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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT05680974 ### Funding Statement This work was supported by grants of the Medical Faculty of the Johannes Kepler University (Linz, Austria), the Swiss National Science Foundation (IZLIZ3_200253/1), the University of Lausanne (SKINTEGRITY.CH collaborative research program), and the Forschungskredit of the University of Zurich (FK-15-040 to WH). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Committee of the Medical Faculty of the Johannes Kepler University Linz and Ethics Committee of the University of Lausanne gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon request to the authors. NanoString and scRNAseq data are available online at GSE222043, GSE235255.