Common antigenicity for two glycosidases

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dc.contributor.authorKakavanos, R.
dc.contributor.authorLehn, P.
dc.contributor.authorCallebaut, I.
dc.contributor.authorMeikle, P.
dc.contributor.authorParkinson-Lawrence, E.
dc.contributor.authorHopwood, J.
dc.contributor.authorBrooks, D.
dc.date.issued2006
dc.descriptionCopyright © 2005 Federation of European Biochemical Societies Published by Elsevier B.V.
dc.description.abstractEnzyme 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.
dc.description.statementofresponsibilityRevecca Kakavanos, Pierre Lehn, Isabelle Callebaut, Peter J. Meikle, Emma J. Parkinson-Lawrence, John J. Hopwood and Doug A. Brooks
dc.description.urihttp://www.elsevier.com/wps/find/journaldescription.cws_home/506085/description#description
dc.identifier.citationFEBS Letters, 2006; 580(1):87-92
dc.identifier.doi10.1016/j.febslet.2005.11.053
dc.identifier.issn0014-5793
dc.identifier.issn1873-3468
dc.identifier.orcidBrooks, D. [0000-0001-9098-3626]
dc.identifier.urihttp://hdl.handle.net/2440/35764
dc.language.isoen
dc.publisherElsevier Science BV
dc.source.urihttps://doi.org/10.1016/j.febslet.2005.11.053
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectGlycogen Storage Disease Type II
dc.subjectMucopolysaccharidosis I
dc.subjectLysosomal Storage Diseases
dc.subjectalpha-Glucosidases
dc.subjectIduronidase
dc.subjectEpitopes
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectEpitope Mapping
dc.titleCommon antigenicity for two glycosidases
dc.typeJournal article
pubs.publication-statusPublished

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