title: Autosomal-dominant chronic mucocutaneous candidiasis with STAT1-mutation can be complicated with chronic active hepatitis and hypothyroidism.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pediatrics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.
authors: Tomohiro
authors: T
authors: Hori
authors: Hidenori
authors: H
authors: Ohnishi
authors: Takahide
authors: T
authors: Teramoto
authors: Kohji
authors: K
authors: Tsubouchi
authors: Takafumi
authors: T
authors: Naiki
authors: Yoshinobu
authors: Y
authors: Hirose
authors: Osamu
authors: O
authors: Ohara
authors: Mariko
authors: M
authors: Seishima
authors: Hideo
authors: H
authors: Kaneko
authors: Toshiyuki
authors: T
authors: Fukao
authors: Naomi
authors: N
authors: Kondo
mesh_terms: D000328:Adult; D001706:Biopsy; D002178:Candidiasis, Chronic Mucocutaneous / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D005799:Genes, Dominant; D019693:Hepatitis, Autoimmune / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D009154:Mutation; D050794:STAT1 Transcription Factor / Q000235:genetics* / Q000276:immunology; D013963:Thyroid Hormones / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D013963:Thyroid Hormones