ArticleGenes and immunity2010
Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin.
Article in Genes and immunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Insulin gene mutations and posttranslational and translocation defects: associations with diabetes.Endocrine · 2020Pooled it
- Genetic basis of Asian diabetes.Journal of diabetes investigation · 2026Review
- Current and Emerging Assays for Measuring Human T-Cell Responses Against Beta-Cell Antigens in Type 1 Diabetes.Biomolecules · 2025Review
- The role of mitochondrial function in the pathogenesis of diabetes.Frontiers in endocrinology · 2025Review
- Genome-wide investigation of VNTR motif polymorphisms in 8,222 genomes: Implications for biological regulation and human traits.Cell genomics · 2024Article
- Breakdown and Repair of Peripheral Immune Tolerance in Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Aire mediates tolerance to insulin through thymic trimming of high-affinity T cell clones.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Linkage analysis using whole exome sequencing data implicates SLC17A1, SLC17A3, TATDN2 and TMEM131L in type 1 diabetes in Kuwaiti families.Scientific reports · 2023Article
- Aire and Fezf2, two regulators in medullary thymic epithelial cells, control autoimmune diseases by regulating TSAs: Partner or complementer?Frontiers in immunology · 2022Review
- Genetic basis of defects in immune tolerance underlying the development of autoimmunity.Frontiers in immunology · 2022Review
- The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetes.Molecular metabolism · 2021Review
- Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?).Nature reviews. Endocrinology · 2021Review
- Review
- Proinsulin-specific T-cell responses correlate with estimated c-peptide and predict partial remission duration in type 1 diabetes.Clinical & translational immunology · 2021Article
- Hybrid Insulin Peptides Are Recognized by Human T Cells in the Context of DRB1*04:01.Diabetes · 2020Article
- Characterization of Proinsulin T Cell Epitopes Restricted by Type 1 Diabetes-Associated HLA Class II Molecules.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- A pilot study of preproinsulin peptides reactivity in Chinese patients with type 1 diabetes.Diabetes/metabolism research and reviews · 2020Article
- The multi-faceted functioning portrait of LRF/ZBTB7A.Human genomics · 2019Review
- Genetic aspects of type 1 diabetes.Annals of pediatric endocrinology & metabolism · 2019Article
- Development and Characterization of a Preclinical Model for the Evaluation of CD205-Mediated Antigen Delivery Therapeutics in Type 1 Diabetes.ImmunoHorizons · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune responses to autoantigens are in part controlled by deletion of autoreactive cells through genetically regulated selection mechanisms. We have directly analyzed peripheral CD4+ proinsulin (PI) 76-90 (SLQPLALEGSLQKRG)-specific T cells using soluble fluorescent major histocompatibility complex class II tetramers. Subjects with type I diabetes and healthy controls with high levels of peripheral proinsulin-specific T cells were characterized by the presence of a disease-susceptible polymorphism in the insulin variable number of tandem repeats (INS-VNTR) gene. Conversely, subjects with a 'protective' polymorphism in the INS-VNTR gene had nearly undetectable levels of proinsulin tetramer-positive T cells. These results strongly imply a direct relationship between genetic control of autoantigen expression and peripheral autoreactivity, in which proinsulin genotype restricts the quantity and quality of the potential T-cell response. Using a modified tetramer to isolate low-avidity proinsulin-specific T cells from subjects with the susceptible genotype, transcript arrays identified several induced pro-apoptotic genes in the control, but not diabetic subjects, likely representing a second peripheral mechanism for maintenance of tolerance to self antigens.
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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.