PDF(Pubmed)
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. The aim of this study was to characterize the cutaneous immune infiltrate in DD skin lesions in detail and to identify new therapeutic targets. Using gene and protein expression profiling assays including scRNA sequencing, we demonstrate enhanced expression of Th17-related genes and cytokines and increased numbers of Th17 cells in six DD patients. We provide evidence that targeting the IL-17/IL-23 axis in a case series of three DD patients with monoclonal antibodies is efficacious with significant clinical improvement. As DD is a chronic, relapsing disease, our findings might pave the way toward additional options for the long-term management of skin inflammation in patients with DD.
摘要：
达里病（DD）是一种罕见的，与ATP2A2基因突变相关的遗传性多器官疾病。DD患者的皮肤受累通常表现为恶臭，发炎的皮肤和反复发作，严重感染。对于这种慢性疾病的长期管理，治疗选择有限且不足。这项研究的目的是详细表征DD皮肤病变中的皮肤免疫浸润，并确定新的治疗靶标。使用基因和蛋白质表达谱分析分析，包括scRNA测序，我们证实6例DD患者中Th17相关基因和细胞因子的表达增强,Th17细胞数量增加.我们提供的证据表明，在三个DD患者的病例系列中，用单克隆抗体靶向IL-17/IL-23轴是有效的，并有显着的临床改善。由于DD是慢性的，复发性疾病，我们的发现可能为DD患者皮肤炎症的长期治疗提供更多选择.
