ArticlePloS one2011
An analysis of the cross-reactivity of autoantibodies to GAD65 and GAD67 in diabetes.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Characteristics of in-vitro phenotypes of glutamic acid decarboxylase 65 autoantibodies in high-titre individuals.Clinical and experimental immunology · 2013Trial
- Structure and dynamics of GAD65 in complex with an autoimmune polyendocrine syndrome type 2-associated autoantibody.Nature communications · 2025Article
- Stiff-person syndrome and related disorders - diagnosis, mechanisms and therapies.Nature reviews. Neurology · 2024Review
- Anti-Islet Autoantibodies in Type 1 Diabetes.International journal of molecular sciences · 2023Review
- Cystic fibrosis autoantibody signatures associate withFrontiers in immunology · 2023Article
- Anti-GAD65 autoantibody levels measured by ELISA and alternative types of immunoassays in relation to neuropsychiatric diseases versus diabetes mellitus type 1.Frontiers in neurology · 2023Article
- Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C.International journal of molecular sciences · 2022Article
- 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
- Fine Mapping of Glutamate Decarboxylase 65 Epitopes Reveals Dependency on Hydrophobic Amino Acids for Specific Interactions.International journal of molecular sciences · 2019Article
- Islet Autoantibodies.Current diabetes reports · 2016Review
- Long latency between GAD-antibody detection and development of limbic encephalitis--a case report.BMC neurology · 2015Article
- Cofactor-dependent conformational heterogeneity of GAD65 and its role in autoimmunity and neurotransmitter homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Advances in the cellular immunological pathogenesis of type 1 diabetes.Journal of cellular and molecular medicine · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAutoantibodies to GAD65 (anti-GAD65) are present in the sera of 70-80% of patients with type 1 diabetes (T1D), but antibodies to the structurally similar 67 kDa isoform GAD67 are rare. Antibodies to GAD67 may represent a cross-reactive population of anti-GAD65, but this has not been formally tested. METHODOLOGY/PRINCIPAL
findingsIn this study we examined the frequency, levels and affinity of anti-GAD67 in diabetes sera that contained anti-GAD65, and compared the specificity of GAD65 and GAD67 reactivity. Anti-GAD65 and anti-GAD67 were measured by radioimmunoprecipitation (RIP) using (125)I labeled recombinant GAD65 and GAD67. For each antibody population, the specificity of the binding was measured by incubation with 100-fold excess of unlabeled GAD in homologous and heterologous inhibition assays, and the affinity of binding with GAD65 and GAD67 was measured in selected sera. Sera were also tested for reactivity to GAD65 and GAD67 by immunoblotting. Of the 85 sera that contained antibodies to GAD65, 28 contained anti-GAD67 measured by RIP. Inhibition with unlabeled GAD65 substantially or completely reduced antibody reactivity with both (125)I GAD65 and with (125)I GAD67. In contrast, unlabeled GAD67 reduced autoantibody reactivity with (125)I GAD67 but not with (125)I GAD65. Both populations of antibodies were of high affinity (>10(10) l/mol).
conclusionsOur findings show that autoantibodies to GAD67 represent a minor population of anti-GAD65 that are reactive with a cross-reactive epitope found also on GAD67. Experimental results confirm that GAD65 is the major autoantigen in T1D, and that GAD67 per se has very low immunogenicity. We discuss our findings in light of the known similarities between the structures of the GAD isoforms, in particular the location of a minor cross-reactive epitope that could be induced by epitope spreading.
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