Foulad Delila Pouldar, Cirillo Nicola, Grando Sergei A
Division of Dermatology, University of California, Los Angeles, CA 90095, USA.
Melbourne Dental School, University of Melbourne, Carlton, VI 3053, Australia.
Biology (Basel). 2023 Feb 23;12(3):354. doi: 10.3390/biology12030354.
The importance of acetylcholine (ACh) in keratinocyte adhesion and acantholysis has been investigated over the last three decades, particularly in the pathophysiology of autoimmune blistering dermatoses. Pemphigus vulgaris (PV) is an autoimmune blistering skin disease where autoantibody-mediated suprabasilar intraepidermal splitting causes flaccid blisters and non-healing erosions of the oral mucosa and sometimes also of the skin. Historically, acantholysis in PV was thought to be driven by anti-desmoglein (Dsg) antibodies. Herein, we describe the role of autoantibodies against keratinocyte muscarinic and nicotinic acetylcholine receptors, as well as the annexin-like molecule pemphaxin that also binds ACh, in the immunopathogenesis of PV. The identification of targets in this disease is important, as they may lead to novel diagnostic and therapeutic options in the future for this potentially deadly disease.
在过去三十年中,人们一直在研究乙酰胆碱(ACh)在角质形成细胞黏附及棘层松解中的作用,尤其是在自身免疫性水疱性皮肤病的病理生理学方面。寻常型天疱疮(PV)是一种自身免疫性水疱性皮肤病,自身抗体介导的基底上层表皮内裂隙会导致口腔黏膜有时也包括皮肤出现松弛水疱和不愈合糜烂。从历史上看,PV中的棘层松解被认为是由抗桥粒芯糖蛋白(Dsg)抗体驱动的。在此,我们描述了抗角质形成细胞毒蕈碱型和烟碱型乙酰胆碱受体的自身抗体,以及同样能结合ACh的膜联蛋白样分子天疱疮素在PV免疫发病机制中的作用。确定该疾病的靶点很重要,因为它们未来可能为这种潜在致命疾病带来新的诊断和治疗选择。