ArticleDiabetologia2013
Alternative splicing and differential expression of the islet autoantigen IGRP between pancreas and thymus contributes to immunogenicity of pancreatic islets but not diabetogenicity in humans.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Article
- Epitope-based precision immunotherapy of Type 1 diabetes.Human vaccines & immunotherapeutics · 2023Article
- Presence of immunogenic alternatively spliced insulin gene product in human pancreatic delta cells.Diabetologia · 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
- Transcriptomic diversity in human medullary thymic epithelial cells.Nature communications · 2022Article
- From Disease and Patient Heterogeneity to Precision Medicine in Type 1 Diabetes.Frontiers in medicine · 2022Review
- Revisiting the Antigen-Presenting Function of β Cells in T1D Pathogenesis.Frontiers in immunology · 2021Review
- Alternative Splicing: A New Cause and Potential Therapeutic Target in Autoimmune Disease.Frontiers in immunology · 2021Review
- There Is Something About Insulin Granules.Diabetes · 2020Article
- Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy.Pharmaceutics · 2020Review
- Review
- Autoreactive T cells in type 1 diabetes.The Journal of clinical investigation · 2017Review
- Where, How, and When: Positioning Posttranslational Modification Within Type 1 Diabetes Pathogenesis.Current diabetes reports · 2016Review
- Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see).Nature reviews. Immunology · 2014Review
- Self-antigen expression in the peripheral immune system: roles in self-tolerance and type 1 diabetes pathogenesis.Current diabetes reports · 2014Review
- The IL-2/IL-2R system: from basic science to therapeutic applications to enhance immune regulation.Immunologic research · 2013Review
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThymic expression of self-antigens during T-lymphocyte development is believed to be crucial for preventing autoimmunity. It has been suggested that G6PC2, the gene encoding islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), is differentially spliced between pancreatic beta cells and the thymus. This may contribute to incomplete elimination of IGRP-specific T lymphocytes in the thymus, predisposing individuals to type 1 diabetes. We tested whether specific splice variation in islets vs thymus correlates with loss of tolerance to IGRP in type 1 diabetes.
methodsExpression of G6PC2 splice variants was compared among thymus, purified medullary thymic epithelial cells and pancreatic islets by RT-PCR. Differential immunogenicity of IGRP splice variants was tested in patients and healthy individuals for autoantibodies and specific cytotoxic T lymphocytes using radiobinding assays and HLA class I multimers, respectively.
resultsPreviously reported G6PC2 splice variants, including full-length G6PC2, were confirmed, albeit that they occurred in both pancreas and thymus, rather than islets alone. Yet, their expression levels were profoundly greater in islets than in thymus. Moreover, three novel G6PC2 variants were discovered that occur in islets only, leading to protein truncations, frame shifts and neo-sequences prone to immunogenicity. However, autoantibodies to novel or known IGRP splice variants did not differ between patients and healthy individuals, and similar frequencies of IGRP-specific cytotoxic T lymphocytes could be detected in both patients with type 1 diabetes and healthy individuals. CONCLUSIONS/
interpretationWe propose that post-transcriptional variation of tissue-specific self-proteins may affect negative thymic selection, although this need not necessarily lead to disease.
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