ArticleDiabetologia2005
Dynamic changes of GAD65 autoantibody epitope specificities in individuals at risk of developing type 1 diabetes.
Article in Diabetologia, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 68 citations in OpenAlex.
- Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program.Diabetic medicine : a journal of the British Diabetic Association · 2014 · on this mapTrial
- Characteristics of in-vitro phenotypes of glutamic acid decarboxylase 65 autoantibodies in high-titre individuals.Clinical and experimental immunology · 2013Trial
- GAD autoantibody epitope pattern after GAD-alum treatment in children and adolescents with type 1 diabetes.Pediatric diabetes · 2012Trial
- Article
- Structure and dynamics of GAD65 in complex with an autoimmune polyendocrine syndrome type 2-associated autoantibody.Nature communications · 2025Article
- Latent autoimmune diabetes in youth.Frontiers in immunology · 2025Review
- Improved Specificity of Glutamate Decarboxylase 65 Autoantibody Measurement Using Luciferase-Based Immunoprecipitation System Assays.Diabetes · 2024Article
- Article
- Anti-Islet Autoantibodies in Type 1 Diabetes.International journal of molecular sciences · 2023Review
- Exploration of Immune Targets for Type 1 Diabetes and Latent Autoimmune Disease Immunotherapy.ImmunoTargets and therapy · 2023Review
- Autoantibodies to N-terminally Truncated GAD65(96-585): HLA Associations and Predictive Value for Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2022Observational
- GAD65 Antibody Epitopes and Genetic Background in Latent Autoimmune Diabetes in Youth (LADY).Frontiers in immunology · 2022Article
- Protein-engineered molecules carrying GAD65 epitopes and targeting CD35 selectively down-modulate disease-associated human B lymphocytes.Clinical and experimental immunology · 2019Article
- Mechanistic basis of immunotherapies for type 1 diabetes mellitus.Translational research : the journal of laboratory and clinical medicine · 2013Review
- Islet autoantigens: structure, function, localization, and regulation.Cold Spring Harbor perspectives in medicine · 2012Review
- Through the fog: recent clinical trials to preserve β-cell function in type 1 diabetes.Diabetes · 2012Review
- GAD65 autoantibodies and its role as biomarker of Type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA).Drugs of the future · 2011Article
- The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Modulation of diabetes in NOD mice by GAD65-specific monoclonal antibodies is epitope specific and accompanied by anti-idiotypic antibodies.Immunology · 2008Article
- Autoantibody epitopes to the smaller isoform of glutamate decarboxylase do not differ in Swedish and Japanese type 1 diabetes patients and may be associated with high-risk human leucocyte antigen class II alleles.Clinical and experimental immunology · 2007Article
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
Abstract
aims/hypothesisProgression to type 1 diabetes is associated with intramolecular epitope spreading to disease-specific antibody epitopes located in the middle region of glutamic acid decarboxylase 65 (GAD65).
methodsThe relationship between intramolecular epitope spreading of autoantibodies specific to GAD65 in relation to the risk of developing type 1 diabetes was tested in 22 high-risk individuals and 38 low-risk individuals. We determined the conformational epitopes in this longitudinal study by means of competition experiments using recombinant Fab of four GAD65-specific monoclonal antibodies.
resultsSera from high-risk children in the preclinical stage recognise a specific combination of GAD65 antibody epitopes located in the middle and the C-terminus of GAD65. High risk of progressing to disease is associated with the emergence of antibodies specific for conformational epitopes at the N-terminus and the middle region. Binding to already established antibody epitopes located in the middle and at the N-terminus increases and shows a significant relation (p=0.005) with HLA, which confers risk of developing diabetes. CONCLUSIONS/
interpretationIn type 1 diabetes, GAD65 antibodies are initially generated against the middle and C-terminal regions of GAD65. In genetically predisposed subjects the autoimmune response may then undergo intramolecular epitope spreading towards epitopes on the N-terminus and further epitopes located in the middle. These findings clearly demonstrate that the GAD65 autoantibody response in the preclinical stage of type 1 diabetes is dynamic and related to the HLA genotypes that confer risk of diabetes. GAD65-specific Fab should prove useful in predicting progression from islet autoimmunity to clinical onset of type 1 diabetes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.