Kakavanos, R.Lehn, P.Callebaut, I.Meikle, P.Parkinson-Lawrence, E.Hopwood, J.Brooks, D.2007-07-102007-07-102006FEBS Letters, 2006; 580(1):87-920014-57931873-3468http://hdl.handle.net/2440/35764Copyright © 2005 Federation of European Biochemical Societies Published by Elsevier B.V.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.enAnimalsHumansMiceGlycogen Storage Disease Type IIMucopolysaccharidosis ILysosomal Storage Diseasesalpha-GlucosidasesIduronidaseEpitopesEnzyme-Linked Immunosorbent AssayEpitope MappingJournal article002006267210.1016/j.febslet.2005.11.0530002346051000172-s2.0-2934446770051456Brooks, D. [0000-0001-9098-3626]