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Journal of Clinical Immunology

, Volume 33, Issue 7, pp 1165–1174 | Cite as

Autosomal Dominant Anhidrotic Ectodermal Dysplasia with Immunodeficiency Caused by a Novel NFKBIA Mutation, p.Ser36Tyr, Presents with Mild Ectodermal Dysplasia and Non-Infectious Systemic Inflammation

  • Takakazu Yoshioka
  • Ryuta Nishikomori
  • Junichi Hara
  • Keiko Okada
  • Yoshiko Hashii
  • Ikuo Okafuji
  • Seishiro Nodomi
  • Tomoki Kawai
  • Kazushi Izawa
  • Hidenori Ohnishi
  • Takahiro Yasumi
  • Tatsutoshi Nakahata
  • Toshio Heike
Original Research

Abstract

Purpose

Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is characterized by hypohidrosis, dental abnormalities, sparse hair, and immunodeficiency. Autosomal dominant (AD)-EDA-ID, caused by a heterozygous mutation within NFKBIA, is very rare and its clinical features remain largely unknown. This study describes a patient with AD-EDA-ID harboring a novel NFKBIA mutation who presented with mild EDA and non-infectious systemic inflammation.

Methods

The clinical presentation of an AD-EDA-ID patient was described and immunological, genetic, and biochemical analyses were performed, with a focus on nuclear factor kappa B (NF-κB) activation.

Results

The patient presented with symptoms of mild EDA-ID, namely sparse hair and hypohidrosis, although a skin biopsy confirmed the presence of sweat glands. There were no dental abnormalities. The patient also suffered from non-infectious inflammation, which responded to systemic corticosteroid therapy; however, the patient remained ill. Immunological analyses revealed reduced Toll-like receptor/IL-1 (TLR/IL-1) and tumor necrosis factor (TNF) receptor family responses to various stimuli. Genetic analysis identified a de novo heterozygous missense mutation, p.Ser36Tyr, in NFKBIA, resulting in defective NFKBIA degradation and impaired NF-κB activation. The patient was diagnosed with AD-EDA-ID and underwent hematopoietic stem cell transplantation. Engraftment was successful, with few signs of acute graft versus host disease. However, the patient suffered hemolytic anemia and thrombocytopenia, and died from a brain hemorrhage due to intractable thrombocytopenia.

Conclusion

AD-EDA-ID patients can present with mild ectodermal dysplasia and non-infectious inflammation, rather than with recurrent infections. Also, hematopoietic stem cell transplantation for AD-EDA-ID is still a clinical challenge.

Keywords

EDA-ID NFKBIA IκBα HSCT 

Notes

Acknowledgments

We thank Takeda Pharmaceutical Inc. for kindly providing us with recombinant human IL-2. We also thank Dr. Jain for providing the recombinant human soluble CD40L and Dr. Utani for providing us with normal fibroblasts. We would like to thank Dr. Momoko Nishikori for help with the EMSA assay. This work was supported by Japan’s Ministry of Health, Labor and Welfare and Japan’s Ministry of Education, Culture, Sports, Science, and Technology.

Conflict of Interest

The authors report no actual or potential conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Takakazu Yoshioka
    • 1
  • Ryuta Nishikomori
    • 1
  • Junichi Hara
    • 2
  • Keiko Okada
    • 2
  • Yoshiko Hashii
    • 3
  • Ikuo Okafuji
    • 1
  • Seishiro Nodomi
    • 1
  • Tomoki Kawai
    • 1
  • Kazushi Izawa
    • 1
  • Hidenori Ohnishi
    • 4
  • Takahiro Yasumi
    • 1
  • Tatsutoshi Nakahata
    • 5
  • Toshio Heike
    • 1
  1. 1.Department of Pediatrics, Graduate School of MedicineKyoto UniversityKyotoJapan
  2. 2.Department of Pediatric Hematology and OncologyOsaka City General HospitalOsakaJapan
  3. 3.Department of Developmental Medicine, Graduate School of MedicineOsaka UniversitySuitaJapan
  4. 4.Department of Pediatrics, Graduate School of MedicineGifu UniversityGifuJapan
  5. 5.Department of Clinical Application, Center for iPS Cell Research and ApplicationKyoto UniversityKyotoJapan

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