IgE-mediated anaphylaxis and allergic reactions to idursulfase in patients with Hunter syndrome

Authors

  • J. Kim,

    1. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    2. The Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea
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  • M. R. Park,

    1. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    2. The Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea
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  • D. S. Kim,

    1. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    2. The Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea
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  • J. O. Lee,

    1. The Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea
    2. The Samsung Biomedical Research Institute, Seoul, Korea
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  • S. H. Maeng,

    1. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • S. Y. Cho,

    1. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Y. Han,

    1. The Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea
    2. The Samsung Biomedical Research Institute, Seoul, Korea
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  • K. Ahn,

    Corresponding author
    1. The Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea
    • Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • D. K. Jin

    Corresponding author
    • Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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    • These authors contributed equally to this work.

  • Edited by: Thomas Bieber

Correspondence

Kangmo Ahn, MD, PhD and Dong-Kyu Jin, MD, PhD, Department of Pediatrics, Samsung Medical Center, 50, Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.

Tel.: +82-2-3410-3530

Fax: +82-2-3410-0043

E-mails: kmaped@skku.edu, and jindk.jin@samsung.com

Abstract

Background

Enzyme replacement therapy (ERT) with recombinant human idursulfase is effective for the treatment of Hunter syndrome, mucopolysaccharidosis (MPS) type II. However, various adverse events can occur by the infusion of idursulfase. The purpose was to evaluate the occurrence of infusion-related allergic reactions, including anaphylaxis, to idursulfase in patients with MPS II receiving ERT and to elucidate its possible mechanism.

Methods

A total of 34 patients with MPS II were enrolled to receive ERT with Elaprase® at a dose of 0.5 mg/kg intravenously once a week. Information regarding the symptoms, frequency, and timing of anaphylaxis during treatment was analyzed. Presence of anti-idursulfase IgE antibody was assessed by skin prick test (SPT) and enzyme-linked immunosorbent assay (ELISA). Western blotting was performed to confirm the reaction between idursulfase and specific IgE.

Results

Three patients (8.8%) showed anaphylaxis by infusion of idursulfase. No deaths occurred during the study. Anti-idursulfase IgE antibody was detected by SPT and ELISA. Immunoblotting with patients’ sera and Elaprase® showed a single band of specific IgE binding to the protein around 70 kD, and idursulfase did not display amino acid sequence homology to known allergens. SPT with idursulfase demonstrated positive results in all patients with anaphylaxis. However, we failed to reveal any risk factors for the development of infusion-related immediate-type allergic reactions.

Conclusions

Anaphylaxis related to infusion of idursulfase is mediated by anti-idursulfase IgE antibody, which might be produced by de novo synthesis. SPT is useful in predicting the occurrence of anti-idursulfase IgE-mediated anaphylaxis during infusion.

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