title: Common antigenicity for two glycosidases.
abstract: 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, alpha-glucosidase (Pompe disease or glycogen storage disease type II, GSD II), and alpha-L-iduronidase (Hurler syndrome, mucopolysaccharidosis type I, MPS I). The linear sequence epitope reactivity of affinity purified polyclonal antibodies to recombinant human alpha-glucosidase and alpha-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 alpha-glucosidase showed cross-reactivity with a catalytic structural element of alpha-L-iduronidase. In a previous study, in MPS I patients who developed an immune response to ERT, this same site on alpha-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.
authors.affiliation: Lysosomal Diseases Research Unit, Department of Genetic Medicine, Children Youth and Women's Health Service, 72 King William Road, North Adelaide, Adelaide, SA 5006, Australia.
authors.forename: Revecca
authors.initials: R
authors.lastname: Kakavanos
authors.forename: Pierre
authors.initials: P
authors.lastname: Lehn
authors.forename: Isabelle
authors.initials: I
authors.lastname: Callebaut
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Parkinson-Lawrence
authors.forename: John J
authors.initials: JJ
authors.lastname: Hopwood
authors.forename: Doug A
authors.initials: DA
authors.lastname: Brooks
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006009:Glycogen Storage Disease Type II / Q000276:immunology / Q000628:therapy; D006801:Humans; D007068:Iduronidase / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D016464:Lysosomal Storage Diseases / Q000276:immunology / Q000628:therapy; D051379:Mice; D008059:Mucopolysaccharidosis I / Q000276:immunology / Q000628:therapy; D000520:alpha-Glucosidases / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D000939:Epitopes; D000520:alpha-Glucosidases; D007068:Iduronidase