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Successful Treatment with Infliximab for Inflammatory Colitis in a Patient with X-linked Anhidrotic Ectodermal Dysplasia with Immunodeficiency

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Abstract

X-linked anhidrotic ectodermal dysplasia with immunodeficiency (X-EDA-ID) is caused by hypomorphic mutations in the gene encoding nuclear factor-κB essential modulator protein (NEMO). Patients are susceptibile to diverse pathogens due to insufficient cytokine and frequently show severe chronic colitis. An 11-year-old boy with X-EDA-ID was hospitalized with autoimmune symptoms and severe chronic colitis which had been refractory to immunosuppressive drugs. Since tumor necrosis factor (TNF) α is responsible for the pathogenesis of NEMO colitis according to intestinal NEMO and additional TNFR1 knockout mice studies, and high levels of TNFα-producing mononuclear cells were detected in the patient due to the unexpected gene reversion mosaicism of NEMO, an anti-TNFα monoclonal antibody was administered to ameliorate his abdominal symptoms. Repeated administrations improved his colonoscopic findings as well as his dry skin along with a reduction of TNFα-expressing T cells. These findings suggest TNF blockade therapy is of value for refractory NEMO colitis with gene reversion.

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Acknowledgments

We profoundly thank for Dr. Kazuko Uno of the Louis-Pasteur Medical Research Center in Japan for support of our experiments and Dr. Maiko Kai and Dr. Naoki Karasawa1 for their warm care of patients. This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Conflict of Interests

The authors declare no competing financial interests.

Author information

Authors and Affiliations

  1. Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan

    Tomoyuki Mizukami, Megumi Obara & Hiroyuki Nunoi

  2. Kumamoto Saishunso National Hospital, Kumamoto, Japan

    Tomoyuki Mizukami

  3. Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Ryuta Nishikomori, Tomoki Kawai & Toshio Heike

  4. Department of Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Yoshihiro Tahara

  5. Department of Pathophysiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Naoki Sameshima & Kousuke Marutsuka

  6. Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Hiroshi Nakase

  7. Division of Medical Oncology, Hematology and Infectious Disease, Department of Medicine, Fukuoka University, Fukuoka, Japan

    Nobuhiro Kimura

Authors
  1. Tomoyuki Mizukami
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  2. Megumi Obara
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  3. Ryuta Nishikomori
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  11. Hiroyuki Nunoi
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Corresponding author

Correspondence to Hiroyuki Nunoi.

Electronic Supplementary Material

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Supplementary Fig. 1

Manifestations of our X-EDA-ID patient. (A) Herpes zoster was seen in his left chest. (B) Hypodontia and conical-shaped teeth at 4 years of age. (C) The radiograph of teeth was taken at 8 years (PPTX 296 kb)

Supplementary Fig. 2

Frequency of TCR Vα and Vβ repertoires in our X-EDA-ID patient. Bar graphs indicate the semiquantitative assessment of TCR V gene usage in peripheral blood T cells (PPTX 63.3 kb)

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Mizukami, T., Obara, M., Nishikomori, R. et al. Successful Treatment with Infliximab for Inflammatory Colitis in a Patient with X-linked Anhidrotic Ectodermal Dysplasia with Immunodeficiency. J Clin Immunol 32, 39–49 (2012). https://doi.org/10.1007/s10875-011-9600-0

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  • DOI: https://doi.org/10.1007/s10875-011-9600-0

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