Common antigenicity for two glycosidases

Revecca Kakavanos, Pierre Lehn, Isabelle Callebaut, Peter J. Meikle, Emma J. Parkinson-Lawrence, John J. Hopwood, Doug A. Brooks

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2 Citations (Scopus)


Enzyme replacement therapy (ERT) has proven to be an effective therapy for some lysosomal storage disorder (LSD) patients. A potential complication during ERT is the generation of an immune response against the replacement protein. We have investigated the antigenicity of two distantly related glycosidases, α-glucosidase (Pompe disease or glycogen storage disease type II, GSD II), and α-l-iduronidase (Hurler syndrome, mucopolysaccharidosis type I, MPS I). The linear sequence epitope reactivity of affinity purified polyclonal antibodies to recombinant human α-glucosidase and α-l-iduronidase was defined, to both glycosidases. The polyclonal antibodies exhibited some cross-reactive epitopes on the two proteins. Moreover, a monoclonal antibody to the active site of α-glucosidase showed cross-reactivity with a catalytic structural element of α-l-iduronidase. In a previous study, in MPS I patients who developed an immune response to ERT, this same site on α-l-iduronidase was highly antigenic and the last to tolerise following repeated enzyme infusions. We conclude that glycosidases can exhibit cross-reactive epitopes, and infer that this may relate to common structural elements associated with their active sites.

Original languageEnglish
Pages (from-to)87-92
Number of pages6
JournalFEBS Letters
Issue number1
Publication statusPublished or Issued - 9 Jan 2006


  • Antibody cross-reactivity
  • Antigenicity
  • Enzyme replacement therapy
  • Epitope reactivity
  • Glycosidase
  • Lysosomal storage disorders

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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