ArticleDiabetologia2015
Antibodies to post-translationally modified insulin in type 1 diabetes.
Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 57 citations in OpenAlex.
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Oxidative Post-Translational Modifications of Insulin in Type 1 Diabetes Autoimmunity.Immunological reviews · 2026Review
- Capillary Electrophoresis Immunoassay for Detection of Anti-insulin Antibodies.Journal of separation science · 2026Article
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Associations Between Dietary Factors, Metabolic Factors, Sleep Disorders, Physical Activity, and the Risk of Multiple Sclerosis: A Univariable and Multivariable Mendelian Randomization Study.Food science & nutrition · 2025Article
- The role of oxidative post-translational modifications in type 1 diabetes pathogenesis.Frontiers in immunology · 2025Review
- Oxidized Melanoma Antigens Promote Activation and Proliferation of Cytotoxic T-Cell Subpopulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Identification of Autoantibodies to a Hybrid Insulin Peptide in Type 1 Diabetes.Diagnostics (Basel, Switzerland) · 2023Article
- Oxidant-modified amylin fibrils and aggregates alter the inflammatory profile of multiple myeloid cell types, but are non-toxic to islet β cells.Redox biology · 2023Article
- Prevaccination Glucose Time in Range Correlates With Antibody Response to SARS-CoV-2 Vaccine in Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2023Article
- Using mass spectrometry to identify neoantigens in autoimmune diseases: The type 1 diabetes example.Seminars in immunology · 2023Review
- Autoantibody and T cell responses to oxidative post-translationally modified insulin neoantigenic peptides in type 1 diabetes.Diabetologia · 2023Article
- Identification of autoantigens and their potential post-translational modification in EGPA and severe eosinophilic asthma.Frontiers in immunology · 2023Article
- Recognition of mRNA Splice Variant and Secretory Granule Epitopes by CD4+ T Cells in Type 1 Diabetes.Diabetes · 2023Article
- Oxidized Proteins Differentially Affect Maturation and Activation of Human Monocyte-Derived Cells.Cells · 2022Article
- Gas Plasma Protein Oxidation Increases Immunogenicity and Human Antigen-Presenting Cell Maturation and Activation.Vaccines · 2022Article
- Setting the Stage for Insulin Granule Dysfunction during Type-1-Diabetes: Is ER Stress the Culprit?Biomedicines · 2022Review
- Posttranslational modifications in diabetes: Mechanisms and functions.Reviews in endocrine & metabolic disorders · 2022Review
- Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity.Diabetes · 2022Article
- Diabetes and COVID-19: Short- and Long-Term Consequences.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2022Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aim/hypothesisInsulin is the most specific beta cell antigen and a potential primary autoantigen in type 1 diabetes. Insulin autoantibodies (IAAs) are the earliest marker of beta cell autoimmunity; however, only slightly more than 50% of children and even fewer adults newly diagnosed with type 1 diabetes are IAA positive. The aim of this investigation was to determine if oxidative post-translational modification (oxPTM) of insulin by reactive oxidants associated with islet inflammation generates neoepitopes that stimulate an immune response in individuals with type 1 diabetes.
methodsoxPTM of insulin was generated using ribose and various reactive oxygen species. Modifications were analysed by SDS-PAGE, three-dimensional fluorescence and MS. Autoreactivity to oxPTM insulin (oxPTM-INS) was observed by ELISA and western blotting, using sera from participants with type 1 or type 2 diabetes and healthy controls as probes. IAA was measured using the gold-standard radiobinding assay (RBA).
resultsMS of oxPTM-INS identified chlorination of Tyr16 and Tyr26; oxidation of His5, Cys7 and Phe24; and glycation of Lys29 and Phe1 in chain B. Significantly higher binding to oxPTM-INS vs native insulin was observed in participants with type 1 diabetes, with 84% sensitivity compared with 61% sensitivity for RBA. oxPTM-INS autoantibodies and IAA co-existed in 50% of those with type 1 diabetes. Importantly 34% of those with diabetes who were IAA negative were oxPTM-INS positive. Altogether, 95% of participants with type 1 diabetes presented with autoimmunity to insulin by RBA, oxPTM-INS or both. Binding to oxPTM-INS was directed towards oxPTM-INS fragments with slower mobility than native insulin. CONCLUSION/
interpretationThese data suggest that oxPTM-INS is a potential autoantigen in individuals with new-onset type 1 diabetes.
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Registered trials
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.