Autosomal-Dominant Chronic Mucocutaneous Candidiasis with STAT1-Mutation can be Complicated with Chronic Active Hepatitis and Hypothyroidism
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- Hori, T., Ohnishi, H., Teramoto, T. et al. J Clin Immunol (2012) 32: 1213. doi:10.1007/s10875-012-9744-6
To describe a case of autosomal-dominant (AD)-chronic mucocutaneous candidiasis (CMC) with a signal transducer and activator of transcription (STAT) 1 gene mutation, and some of the important complications of this disease such as chronic hepatitis.
We present a 23-year-old woman with CMC, chronic active hepatitis, and hypothyroidism. Her father also had CMC. We performed several immunological analyses of blood and liver samples, and searched for gene mutations for CMC in the patient and her father.
We identified the heterozygous substitution c.821 G > A (p.Arg274Gln) in the STAT1 gene of both the patient and her father. The level of β-glucan induced interferon (IFN)-γ in her blood cells was significantly low. Immunoblot analysis detected serum anti-interleukin (IL)-17 F autoantibody. She was found to have increased (low-titer) antibodies related to her hypothyroidism and hepatitis. Her serum IL-18 levels fluctuated with her AST and ALT levels. Liver biopsy revealed CD68-positive cell infiltration and IL-18 expression in the sinusoidal regions. These results suggest that the chronic active hepatitis in this patient may be exacerbated by the excessive IL-18 accumulation caused by recurrent mucocutaneous fungal infection, and decreased IFN-γ production.
AD-CMC is known to be caused by a gain-of-function mutation of the STAT1 gene. Chronic active hepatitis is a rare complication of AD-CMC, with currently unknown pathogenesis. It seems that the clinical phenotype in this patient is modified by autoimmune mechanisms and cytokine dysregulation. AD-CMC can be complicated by various immune disorders including autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
KeywordsAD-CMCSTAT1hypothyroidismchronic active hepatitisanti-IL-17 F autoantibodyIL-18
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
Anti-smooth muscle antibody
Caspase recruitment domain-containing protein
Chronic mucocutaneous candidiasis
Dedicator of cytokinesis
Interferon-γ activating factor
Interferon-stimulated-γ factor 3
Liver-kidney microsome 1
Mendelian susceptibility to mycobacterial disease
Peripheral blood mononuclear cells
Signal transducer and activator of transcription
Tumor necrosis factor
Anti-thyroid peroxidase antibody
Thyroid stimulating hormone blocking antibody