title: Treatment options for chronic mucocutaneous candidiasis.
abstract: Autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) is a rare and severe primary immunodeficiency that is characterized by mucocutaneous fungal infection, autoimmunity, cerebral aneurysms, and oropharyngeal and esophageal cancer. Recently, it was discovered that STAT1 mutations are responsible for AD-CMC. These mutations lead to the inability of STAT1 to be dephosphorylated, resulting in hyperphosphorylation, increased binding to the DNA, and gain of function (GOF) effects on STAT1 signaling. Furthermore, a characteristic feature of AD-CMC patients is deficiency in the T-helper 17 (Th17) responses, which is believed to be the immunological cause of the mucocutaneous fungal infection. No targeted treatment other than lifelong antifungal prophylaxis exists for AD-CMC. However, the discovery of the genetic and immunological defects makes it now possible to explore new treatment strategies. This review will discuss immunomodulatory treatment options that can be explored in patients with STAT1 GOF mutations.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Center for Infectious Diseases (RCI), The Netherlands. Electronic address: frank.vandeveerdonk@radboudumc.nl.
authors.forename: Frank L
authors.initials: FL
authors.lastname: van de Veerdonk
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Center for Infectious Diseases (RCI), The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000628:therapy*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000382:microbiology*; D056747:Immunomodulation; D009154:Mutation; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology
chemical_list: D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human
keywords: Fungal infection; Gain of function; Immunodeficiency; STAT1; Therapy; Treatment