scholarly journals Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis

2015 ◽  
Vol 212 (5) ◽  
pp. 619-631 ◽  
Author(s):  
Yun Ling ◽  
Sophie Cypowyj ◽  
Caner Aytekin ◽  
Miguel Galicchio ◽  
Yildiz Camcioglu ◽  
...  
Keyword(s):  
Cell Surface ◽  
Candida Species ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Cellular Responses ◽  
Chronic Mucocutaneous Candidiasis ◽  
Persistent Infections ◽  
Mucocutaneous Candidiasis

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections of the skin, nail, oral, and genital mucosae with Candida species, mainly C. albicans. Autosomal-recessive (AR) IL-17RA and ACT1 deficiencies and autosomal-dominant IL-17F deficiency, each reported in a single kindred, underlie CMC in otherwise healthy patients. We report three patients from unrelated kindreds, aged 8, 12, and 37 yr with isolated CMC, who display AR IL-17RC deficiency. The patients are homozygous for different nonsense alleles that prevent the expression of IL-17RC on the cell surface. The defect is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. However, in contrast to what is observed for the IL-17RA– and ACT1-deficient patients tested, the response to IL-17E (IL-25) is maintained in these IL-17RC–deficient patients. These experiments of nature indicate that human IL-17RC is essential for mucocutaneous immunity to C. albicans but is otherwise largely redundant.

scholarly journals Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis

2011 ◽  
Vol 208 (8) ◽  
pp. 1635-1648 ◽  
Author(s):  
Luyan Liu ◽  
Satoshi Okada ◽  
Xiao-Fei Kong ◽  
Alexandra Y. Kreins ◽  
Sophie Cypowyj ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Coiled Coil ◽  
Cellular Responses ◽  
Chronic Mucocutaneous Candidiasis ◽  
Loss Of Function ◽  
Gain Of Function ◽  
Mucocutaneous Candidiasis ◽  
Coiled Coil Domain ◽  
Whole Exome ◽  
Ifn Γ

Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity.

STAT1Mutations in Autosomal Dominant Chronic Mucocutaneous Candidiasis

2011 ◽  
Vol 365 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Frank L. van de Veerdonk ◽  
Theo S. Plantinga ◽  
Alexander Hoischen ◽  
Sanne P. Smeekens ◽  
Leo A.B. Joosten ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Chronic Mucocutaneous Candidiasis ◽  
Mucocutaneous Candidiasis

scholarly journals STAT1 Hyperphosphorylation and Defective IL12R/IL23R Signaling Underlie Defective Immunity in Autosomal Dominant Chronic Mucocutaneous Candidiasis

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e29248 ◽  
Author(s):  
Sanne P. Smeekens ◽  
Theo S. Plantinga ◽  
Frank L. van de Veerdonk ◽  
Bas Heinhuis ◽  
Alexander Hoischen ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Chronic Mucocutaneous Candidiasis ◽  
Mucocutaneous Candidiasis

scholarly journals Intracranial Calcifications in Autoimmune Polyendocrine Ectodermal Dystrophy Syndrome (APECED): About A Case Report

2021 ◽  
pp. 1-3
Author(s):  
Benfaddoul O ◽  
◽  
Zouita B ◽  
El azzouzi B ◽  
Basraoui N ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Chronic Mucocutaneous Candidiasis ◽  
Type I ◽  
Syndrome Type ◽  
Autoimmune Polyglandular Syndrome ◽  
Mucocutaneous Candidiasis ◽  
Autoimmune Polyendocrinopathy ◽  
Life Threatening ◽  
Autoimmune Polyglandular Syndrome Type

Autoimmune polyendocrinopathy ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type I (APS I), is an uncommon, but debilitating autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE), It is characterized by a broad and diverse clinical spectrum which can lead to severe metabolic alterations and eventually life-threatening events. Hypoparathyroidism is one of the major criteria for clinical diagnosis, in addition to chronic mucocutaneous candidiasis and autoimmune adrenal insufficiency. This component is responsible for the forming of brain calcifications which tend to have a characteristic predilection for the basal ganglia. In this article, we report an additional case to the literature and provide a literature review of the expanding radiological spectrum of this syndrome

Autosomal-Dominant Chronic Mucocutaneous Candidiasis with STAT1-Mutation can be Complicated with Chronic Active Hepatitis and Hypothyroidism

2012 ◽  
Vol 32 (6) ◽  
pp. 1213-1220 ◽  
Author(s):  
Tomohiro Hori ◽  
Hidenori Ohnishi ◽  
Takahide Teramoto ◽  
Kohji Tsubouchi ◽  
Takafumi Naiki ◽  
...  
Keyword(s):  
Chronic Active Hepatitis ◽  
Autosomal Dominant ◽  
Chronic Mucocutaneous Candidiasis ◽  
Mucocutaneous Candidiasis
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