ArticleDiabetologia2020
Clinical and genetic correlates of islet-autoimmune signatures in juvenile-onset type 1 diabetes.
Article in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- The central role of the β-cell in diabetes: from monogenic forms to type 1, type 2, and gestational diabetes.Reviews in endocrine & metabolic disorders · 2026Review
- Limited efficacy of a therapeutic anti-CD40 monoclonal antibody to inhibit activated CD4 T cell autoimmunity in vitro.PloS one · 2026Article
- New Perspectives in Studying Type 1 Diabetes Susceptibility Biomarkers.International journal of molecular sciences · 2025Review
- Current and Emerging Assays for Measuring Human T-Cell Responses Against Beta-Cell Antigens in Type 1 Diabetes.Biomolecules · 2025Review
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Review
- Neutrophil Extracellular Traps (NETs) in Sterile Inflammatory Diseases.Journal of inflammation research · 2025Review
- Advancing Animal Models of Human Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Assisting the implementation of screening for type 1 diabetes by using artificial intelligence on publicly available data.Diabetologia · 2024Article
- Down Syndrome and Autoimmune Disease.Clinical reviews in allergy & immunology · 2024Review
- The role of GABA in type 1 diabetes.Frontiers in endocrinology · 2024Review
- Islet autoimmunity in human type 1 diabetes: initiation and progression from the perspective of the beta cell.Diabetologia · 2023Review
- GABA and Combined GABA with GAD65-Alum Treatment Alters Th1 Cytokine Responses of PBMCs from Children with Recent-Onset Type 1 Diabetes.Biomedicines · 2023Article
- The need and benefit of immune monitoring to define patient and disease heterogeneity, mechanisms of therapeutic action and efficacy of intervention therapy for precision medicine in type 1 diabetes.Frontiers in immunology · 2023Article
- Review
- Circulating platelet-neutrophil aggregates characterize the development of type 1 diabetes in humans and NOD mice.JCI insight · 2022Article
- From Disease and Patient Heterogeneity to Precision Medicine in Type 1 Diabetes.Frontiers in medicine · 2022Review
- The Contribution of Neutrophils and NETs to the Development of Type 1 Diabetes.Frontiers in immunology · 2022Review
- Functional Impact of Risk Gene Variants on the Autoimmune Responses in Type 1 Diabetes.Frontiers in immunology · 2022Review
- Human islet T cells are highly reactive to preproinsulin in type 1 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisHeterogeneity in individuals with type 1 diabetes has become more generally appreciated, but has not yet been extensively and systematically characterised. Here, we aimed to characterise type 1 diabetes heterogeneity by creating immunological, genetic and clinical profiles for individuals with juvenile-onset type 1 diabetes in a cross-sectional study.
methodsParticipants were HLA-genotyped to determine HLA-DR-DQ risk, and SNP-genotyped to generate a non-HLA genetic risk score (GRS) based on 93 type 1 diabetes-associated SNP variants outside the MHC region. Islet autoimmunity was assessed as T cell proliferation upon stimulation with the beta cell antigens GAD65, islet antigen-2 (IA-2), preproinsulin (PPI) and defective ribosomal product of the insulin gene (INS-DRIP). Clinical parameters were collected retrospectively.
resultsOf 80 individuals, 67 had proliferation responses to one or more islet antigens, with vast differences in the extent of proliferation. Based on the multitude and amplitude of the proliferation responses, individuals were clustered into non-, intermediate and high responders. High responders could not be characterised entirely by enrichment for the highest risk HLA-DR3-DQ2/DR4-DQ8 genotype. However, high responders did have a significantly higher non-HLA GRS. Clinically, high T cell responses to beta cell antigens did not reflect in worsened glycaemic control, increased complications, development of associated autoimmunity or younger age at disease onset. The number of beta cell antigens that an individual responded to increased with disease duration, pointing to chronic islet autoimmunity and epitope spreading. CONCLUSIONS/
interpretationCollectively, these data provide new insights into type 1 diabetes disease heterogeneity and highlight the importance of stratifying patients on the basis of their genetic and autoimmune signatures for immunotherapy and personalised disease management.
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