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https://hdl.handle.net/2440/35764
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Type: | Journal article |
Title: | Common antigenicity for two glycosidases |
Author: | Kakavanos, R. Lehn, P. Callebaut, I. Meikle, P. Parkinson-Lawrence, E. Hopwood, J. Brooks, D. |
Citation: | FEBS Letters, 2006; 580(1):87-92 |
Publisher: | Elsevier Science BV |
Issue Date: | 2006 |
ISSN: | 0014-5793 1873-3468 |
Statement of Responsibility: | Revecca Kakavanos, Pierre Lehn, Isabelle Callebaut, Peter J. Meikle, Emma J. Parkinson-Lawrence, John J. Hopwood and Doug A. Brooks |
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. |
Keywords: | Animals Humans Mice Glycogen Storage Disease Type II Mucopolysaccharidosis I Lysosomal Storage Diseases alpha-Glucosidases Iduronidase Epitopes Enzyme-Linked Immunosorbent Assay Epitope Mapping |
Description: | Copyright © 2005 Federation of European Biochemical Societies Published by Elsevier B.V. |
DOI: | 10.1016/j.febslet.2005.11.053 |
Description (link): | http://www.elsevier.com/wps/find/journaldescription.cws_home/506085/description#description |
Published version: | http://dx.doi.org/10.1016/j.febslet.2005.11.053 |
Appears in Collections: | Aurora harvest 6 Paediatrics publications |
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