Journal of Clinical Immunology

, Volume 39, Issue 6, pp 596–599 | Cite as

Chronic Mucocutaneous Candidiasis in an Adolescent Boy Due to a Novel Mutation in TRAF3IP2

  • Sagar BhattadEmail author
  • Chitra Dinakar
  • Haneesha Pinnamaraju
  • Aparna Ganapathy
  • Ashraf Mannan
Original Article



IL-17-mediated signaling is crucial in defense against fungi and bacteria. Defective Th17 immunity has been implicated in a group of disorders called chronic mucocutaneous candidiasis (CMC). TRAF3IP2 is an adaptor protein involved in downstream signaling for IL-17 receptors.


An 18-year-old boy, product of consanguineous wedlock, presented with history of repeated episodes of oral thrush and recurrent pneumonia from first year of life. On examination, he was wasted and had oral thrush and abnormal dentition; grade 2 clubbing and respiratory system examination revealed coarse crepitations. On evaluation, HIV status was negative and basic immunological screen was unrewarding. Genetic testing by next-generation sequencing showed a novel homozygous mutation in TRAF3IP2 gene not reported to date. The defect is likely to cause ACT1 deficiency. He was started on antibiotic and antifungal prophylaxis and remains well on follow-up.


We describe an adolescent boy with recurrent oral candidiasis and bronchiectasis due to a novel mutation in TRAF3IP2 gene, not reported to date. This is also the only second report of CMC due to ACT1 deficiency.


Mucocutaneous candidiasis TRAF3IP2 ACT1 immune deficiency 



We acknowledge Dr. Biman Saikia and Dr. Smrity Sahu, Department of Immunopathology, PGIMER, Chandigarh, India, for performing the Th17 analysis in the index case.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

10875_2019_664_MOESM1_ESM.docx (44 kb)
ESM 1 (DOCX 43 kb)


  1. 1.
    Okada S, Puel A, Casanova JL, Kobayashi M. Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity. Clin Transl Immunol. 2016;5(12):e114.CrossRefGoogle Scholar
  2. 2.
    Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK, et al. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science. 2011;332(6025):65–8.CrossRefGoogle Scholar
  3. 3.
    Okada S, Kong XF, Kreins AY, Cypowyj S, Abhyankar A, et al. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med. 2011;208(8):1635–48.CrossRefGoogle Scholar
  4. 4.
    Li J, Casanova JL, Puel A. Mucocutaneous IL-17 immunity in mice and humans: host defense vs. excessive inflammation. Mucosal Immunol. 2018 May;11(3):581–9.CrossRefGoogle Scholar
  5. 5.
    Puel A, Döffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med. 2010;207(2):291–7.CrossRefGoogle Scholar
  6. 6.
    Mengesha BG, Conti HR. The role of IL-17 in protection against mucosal Candida infections. J Fungi (Basel). 2017;3(4):52.Google Scholar
  7. 7.
    Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF, Jane-Wit D, et al. The adaptor ACT1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol. 2007;8(3):247–56.CrossRefGoogle Scholar
  8. 8.
    Mannan AU, Singh J, Lakshmikeshava R, Thota N, Singh S, Sowmya TS, et al. Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India. J Hum Genet. 2016;61(6):515–22.CrossRefGoogle Scholar
  9. 9.
    Hüffmeier U, Uebe S, Ekici AB, Bowes J, Giardina E, Korendowych E, et al. Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nat Genet. 2010;42(11):996–9.CrossRefGoogle Scholar
  10. 10.
    Gu C, Wu L, Li X. IL-17 family: cytokines, receptors and signaling. Cytokine. 2013;64(2):477–85.CrossRefGoogle Scholar
  11. 11.
    Maquat LE. Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat Rev Mol Cell Biol. 2004;5(2):89–99.CrossRefGoogle Scholar
  12. 12.
    Doyle MS, Collins ES, FitzGerald OM, Pennington SR. New insight into the functions of the interleukin-17 receptor adaptor protein ACT1 in psoriatic arthritis. Arthritis Res Ther. 2012;14(5):226.CrossRefGoogle Scholar
  13. 13.
    Matsushima Y, Kikkawa Y, Takada T, Matsuoka K, Seki Y, Yoshida H, et al. An atopic dermatitis-like skin disease with hyper-IgE-emia develops in mice carrying a spontaneous recessive point mutation in the Traf3ip2 (ACT1/CIKS) gene. J Immunol. 2010;185(4):2340–9.CrossRefGoogle Scholar
  14. 14.
    Boisson B, Wang C, Pedergnana V, Wu L, Cypowyj S, Rybojad M, et al. An ACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis. Immunity. 2013;39(4):676–86.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pediatric Immunology and Rheumatology Division, Department of PediatricsAster CMI HospitalBangaloreIndia
  2. 2.Department of PediatricsSt. John’s Medical College HospitalBangaloreIndia
  3. 3.Strand Life SciencesBangaloreIndia

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