ArticleClinical and experimental immunology2001
Islet glutamic acid decarboxylase modified by reactive oxygen species is recognized by antibodies from patients with type 1 diabetes mellitus.
Article in Clinical and experimental immunology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- The Role of Iron in Type 1 Diabetes Etiology: A Systematic Review of New Evidence on a Long-Standing Mystery.The review of diabetic studies : RDSPooled it
- Discovery of Post-Translationally Modified Epitopes in Autoimmunity: Someone Has to Fish so Everyone Can Eat.Immunological reviews · 2026Review
- Beyond bystanders: How β cell stress shapes the autoimmune response in T1D.Science translational medicine · 2026Review
- Neurological impairment and hyperglycemia following acute copper sulfate poisoning: a case report.Frontiers in medicine · 2026Article
- The role of oxidative post-translational modifications in type 1 diabetes pathogenesis.Frontiers in immunology · 2025Review
- Residual hyperglycemia after successful treatment of a patient with severe copper sulfate poisoning.Journal of Zhejiang University. Science. B · 2024Article
- Metabolic Syndrome: A Narrative Review from the Oxidative Stress to the Management of Related Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Identification of Autoantibodies to a Hybrid Insulin Peptide in Type 1 Diabetes.Diagnostics (Basel, Switzerland) · 2023Article
- Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity.Diabetes · 2022Article
- Oxygen reactivity with pyridoxal 5'-phosphate enzymes: biochemical implications and functional relevance.Amino acids · 2020Review
- Biological Activities of Selected Plants and Detection of Bioactive Compounds fromMolecules (Basel, Switzerland) · 2020Article
- The Role of β Cell Stress and Neo-Epitopes in the Immunopathology of Type 1 Diabetes.Frontiers in endocrinology · 2020Review
- PROOXIDANT ACTIVITIES OF ANTIOXIDANTS AND THEIR IMPACT ON HEALTH.Acta clinica Croatica · 2019Review
- Redox-Sensitive Innate Immune Pathways During Macrophage Activation in Type 1 Diabetes.Antioxidants & redox signaling · 2018Review
- Optimizing Multiplexed Detections of Diabetes Antibodies via Quantitative Microfluidic Droplet Array.Small (Weinheim an der Bergstrasse, Germany) · 2017Article
- High Neonatal Blood Iron Content Is Associated with the Risk of Childhood Type 1 Diabetes Mellitus.Nutrients · 2017Article
- Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children.Diabetologia · 2017Article
- An immunohistochemical study of nitrotyrosine expression in pancreatic islets of cases with increasing duration of type 1 diabetes and without diabetes.Histochemistry and cell biology · 2017Article
- Where, How, and When: Positioning Posttranslational Modification Within Type 1 Diabetes Pathogenesis.Current diabetes reports · 2016Review
- Antibodies to post-translationally modified insulin in type 1 diabetes.Diabetologia · 2015Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The generation of an autoimmune response against islet beta-cells is central to the pathogenesis of type 1 diabetes mellitus, and this response is driven by the stimulation of autoreactive lymphocytes by components of the beta-cells themselves. Reactive oxygen species (ROS) have been implicated in the beta-cell destruction which leads to type 1 diabetes and may modify beta-cell components so as to enhance their immunogenicity. We investigated the effects of oxidation reactions catalysed by copper or iron on the major beta-cell autoantigen glutamic acid decarboxylase (GAD). Lysates of purified rat islets were exposed to copper or iron sulphate with or without hydrogen peroxide or ascorbic acid. Immunostaining showed that these treatments generated high molecular weight covalently linked aggregates containing GAD. These are not formed by intermolecular disulphide bonds between cysteine residues since they cannot be resolved into monomeric form when electrophoresed under extreme reducing conditions. There was no modification of insulin or pro-insulin by ROS. The same oxidative changes to GAD could be induced in viable islet cells treated with copper sulphate and hydrogen peroxide, and thus the modifications are not an artefact of the catalysed oxidation of cell-free lysates. Sera from patients with type 1 diabetes and stiffman syndrome containing GAD antibodies reacted predominantly with the highest molecular weight modified protein band of GAD: normal human sera did not precipitate GAD. Thus, oxidatively modified aggregates of GAD react with serum antibodies of type 1 diabetes patients and some SMS patients: this is consistent with oxidative modifications of autoantigens being relevant to the pathogenesis of type 1 diabetes.
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