ArticleDiabetologia2019
Proinsulin peptide promotes autoimmune diabetes in a novel HLA-DR3-DQ2-transgenic murine model of spontaneous disease.
Article in Diabetologia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- The origin of autoimmune diseases: is there a role for ancestral HLA-II haplotypes in immune hyperactivity.Frontiers in immunology · 2025Review
- Peripheral blood mononuclear cells reactivity in recent-onset type I diabetes patients is directed against the leader peptide of preproinsulin, GAD65Frontiers in immunology · 2023Article
- Epitope Mapping of Pathogenic Autoantigens on Sjögren's Syndrome-Susceptible Human Leukocyte Antigens Using In Silico Techniques.Journal of clinical medicine · 2022Article
- Preclinical Models to Evaluate the Human Response to Autoantigen and Antigen-Specific Immunotherapy in Human Type 1 Diabetes.Frontiers in endocrinology · 2022Review
- A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes.Frontiers in immunology · 2021Article
- The making of insulin in health and disease.Diabetologia · 2020Review
- Distinct secretion pattern of serum proinsulin in different types of diabetes.Annals of translational medicine · 2020Article
Corrections and comments
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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
aims/hypothesisThe molecular basis for the pathological impact of specific HLA molecules on autoimmune diseases such as type 1 diabetes remains unclear. Recent natural history studies in children have indicated a link between specific HLA genotypes and the first antigenic target against which immune responses develop. We set out to examine this link in vivo by exploring the diabetogenicity of islet antigens on the background of a common diabetes-associated HLA haplotype.
methodsWe generated a novel HLA-transgenic mouse model that expresses high-risk genes for type 1 diabetes (DRB1*03:01-DQA1*05:01-DQB1*02:01) as well as human CD80 under the rat insulin promoter and human CD4, on a C57BL/6 background. Adjuvanted antigen priming was used to reveal the diabetogenicity of candidate antigens and peptides.
resultsHLA-DR3-DQ2 CONCLUSIONS/
interpretationOur study identifies a proinsulin-derived peptide region that is highly diabetogenic on the HLA-DR3-DQ2 background using an in vivo model. This approach and the peptide region identified may have wider implications for future studies of human type 1 diabetes.
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