title: Enzyme replacement therapy in a patient with Fabry disease and the development of IgE antibodies against agalsidase beta but not agalsidase alpha.
abstract: Fabry disease is an X-linked inherited lysosomal storage disorder caused by an inborn deficiency of the enzyme α-galactosidase A. Enzyme replacement therapy (ERT) with agalsidase alpha or beta isozymes is an effective treatment. Cross-reactivity of immunoglobulin G (IgG) antibodies with agalsidase alpha and beta has been reported, but no such reaction has been recorded for IgE antibodies. We present the case of a patient with Fabry disease who developed antiagalsidase beta IgE antibodies without cross-reactivity to agalsidase alpha. A 17-year-old boy with Fabry disease had suffered from severe atopic dermatitis since infancy, and he complained for several years of peripheral pain during the summer months and when exercising. Fabry disease was confirmed by family history and a positive enzyme test, and ERT was commenced. Following infusion of agalsidase beta (1.0 mg/kg), the patient complained of a high temperature in his hands and feet, and purulent eczema developed. The infusion dose was reduced to 0.2 mg/kg, but the hyperthermia did not change, although its duration decreased. After three infusions, eosinophilia developed (9.4%; 573 cells/μl blood) and remained unresolved after four infusions with agalsidase beta. Treatment with this enzyme was discontinued, and agalsidase alpha (0.2 mg/kg) started. This produced immediate resolution of the eosinophilia, which has been maintained during follow-up. In conclusion, this patient developed IgE antibodies against agalsidase beta, which demonstrated no cross-reactivity to agalsidase alpha. These findings emphasize the importance of analyzing IgE antibodies against both enzymes when patients exhibit severe infusion-related events.
authors.affiliation: Department of Pediatrics, Osaka City University, Graduate School of Medicine, Osaka, Japan. akemi-chan@med.osaka-cu.ac.jp
authors.forename: Akemi
authors.initials: A
authors.lastname: Tanaka
authors.forename: Taisuke
authors.initials: T
authors.lastname: Takeda
authors.forename: Takao
authors.initials: T
authors.lastname: Hoshina
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Fukai
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Yamano
mesh_terms: D000293:Adolescent; D000918:Antibody Specificity; D003429:Cross Reactions; D003875:Drug Eruptions / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D057915:Drug Substitution; D056947:Enzyme Replacement Therapy / Q000009:adverse effects*; D004802:Eosinophilia / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D000795:Fabry Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D005334:Fever / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007527:Isoenzymes / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D007073:Immunoglobulin E; D000519:alpha-Galactosidase; C459420:agalsidase beta