Journal of Clinical Immunology

, Volume 32, Issue 6, pp 1213–1220 | Cite as

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

  • Tomohiro Hori
  • Hidenori OhnishiEmail author
  • Takahide Teramoto
  • Kohji Tsubouchi
  • Takafumi Naiki
  • Yoshinobu Hirose
  • Osamu Ohara
  • Mariko Seishima
  • Hideo Kaneko
  • Toshiyuki Fukao
  • Naomi Kondo
Original Research



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.


AD-CMC STAT1 hypothyroidism chronic active hepatitis anti-IL-17 F autoantibody IL-18 



Autosomal dominant


Autoimmune regulator


Antinuclear antibody


Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy


Autosomal recessive


Anti-smooth muscle antibody


Caspase recruitment domain-containing protein


Chronic mucocutaneous candidiasis


Dedicator of cytokinesis


Interferon-γ activating factor


Hyper-IgE syndrome






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



We thank Dr. K. Kubota, Dr. T. Yamamoto, and K. Kasahara for their advice and technical help. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan and by Health and Labour Science Research Grants for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan. The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Tomohiro Hori
    • 1
  • Hidenori Ohnishi
    • 1
    Email author
  • Takahide Teramoto
    • 1
  • Kohji Tsubouchi
    • 2
  • Takafumi Naiki
    • 3
  • Yoshinobu Hirose
    • 4
  • Osamu Ohara
    • 5
    • 6
  • Mariko Seishima
    • 7
  • Hideo Kaneko
    • 8
  • Toshiyuki Fukao
    • 1
  • Naomi Kondo
    • 1
  1. 1.Department of PediatricsGraduate School of Medicine, Gifu UniversityGifuJapan
  2. 2.Department of PediatricsChuno Kosei HospitalGifuJapan
  3. 3.Department of GastroenterologyGraduate School of Medicine, Gifu UniversityGifuJapan
  4. 4.Department of PathologyGifu University HospitalGifuJapan
  5. 5.Laboratory for Immunogenomics, RIKEN Research Center for Allergy and ImmunologyYokohamaJapan
  6. 6.Department of Human Genome ResearchKazusa DNA Research InstituteKisarazuJapan
  7. 7.Department of DermatologyGraduate School of Medicine, Gifu UniversityGifuJapan
  8. 8.Department of Clinical ResearchNagara Medical CenterGifuJapan

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