ArticleClinical and experimental immunology2002
Distinct antigenic features of linear epitopes at the N-terminus and C-terminus of 65 kDa glutamic acid decarboxylase (GAD65): implications for autoantigen modification during pathogenesis.
Article in Clinical and experimental immunology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 28 citations in OpenAlex.
- Stiff-person Syndrome and GAD Antibody-spectrum Disorders: GABAergic Neuronal Excitability, Immunopathogenesis and Update on Antibody Therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- GAD antibody-spectrum disorders: progress in clinical phenotypes, immunopathogenesis and therapeutic interventions.Therapeutic advances in neurological disorders · 2021Review
- High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients.Molecular & cellular proteomics : MCP · 2016Article
- Rat β₃-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- Identification of new autoantigens by protein array indicates a role for IL4 neutralization in autoimmune hepatitis.Molecular & cellular proteomics : MCP · 2012Article
- An analysis of the cross-reactivity of autoantibodies to GAD65 and GAD67 in diabetes.PloS one · 2011Article
- Mapping of human autoantibody binding sites on the calcium-sensing receptor.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2010Article
- Purification of polyclonal anti-conformational antibodies for use in affinity selection from random peptide phage display libraries: a study using the hydatid vaccine EG95.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2009Article
- Post-translational protein modifications in type 1 diabetes: a role for the repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase?Diabetologia · 2007Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
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Abstract
Autoantibodies to 65 kDa glutamic acid decarboxylase (GAD65) are produced in many patients with autoimmune polyendocrine syndrome type II (APS-II) or stiff-man syndrome (SMS) and are heterogeneous in their epitope specificities, recognizing both conformational and linear determinants. Major linear epitopes of GAD, which are recognized by autoantibodies in a minority of these patients, occur in the N-terminal and C-terminal regions. We have investigated antibody recognition of the N- and C-termini of GAD65 in relation to their structural features as an approach to understanding what modifications to the native GAD structure may occur that facilitate the generation of antibodies specific to linear epitopes in these regions during the autoimmune pathogenesis. A monoclonal antibody specific to the N-terminus of GAD65 bound both native and denatured GAD in ELISA, whereas monoclonal and polyclonal antibodies specific to the C-terminus of GAD bound only denatured GAD. These antibodies were epitope mapped using random peptide phage-display libraries and the epitopes related to a previously proposed structural model of GAD65. This has led us to propose that the alpha-helical secondary structure of the C-terminus of GAD65 must be denatured to generate linear epitopes. In contrast, the N-terminus is both surface exposed and linear in the native structure, but may be masked by membrane interactions, which must be broken to facilitate recognition by B cells.
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