Treatment options for chronic mucocutaneous candidiasis - 21/06/16

Doi : 10.1016/j.jinf.2016.04.023

Frank L. van de Veerdonk ^a,^b,^⁎ , Mihai G. Netea ^a,^b
^a Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
^b Radboud Center for Infectious Diseases (RCI), The Netherlands

^∗Corresponding author. Department of Internal Medicine (463), Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +31 24 3618819; fax: +31 24 3541734.Department of Internal Medicine (463)Radboud University Nijmegen Medical CenterP.O. Box 9101Nijmegen6500 HBThe Netherlands

Summary

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.

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Keywords : Therapy, STAT1, Gain of function, Treatment, Fungal infection, Immunodeficiency