ArticleJournal of autoimmunity2017
Flexible peptide recognition by HLA-DR triggers specific autoimmune T-cell responses in autoimmune thyroiditis and diabetes.
Article in Journal of autoimmunity, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Dynamic biomarkers indicate the immunological benefits provided by Ganoderma spore powder in post-operative breast and lung cancer patients.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Trial
- Endocrine-Metabolic Crosstalk Between Diabetes Mellitus and Hypothyroidism: From Network Mechanisms to Translational Stratification.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Cell-intrinsic functions of PD-L1 activate autophagy and prevent cytokine-induced apoptosis.Science advances · 2026Article
- Thyroid autoimmunity in relation to islet autoantibodies in newly diagnosed type 1 diabetes mellitus in children and adolescents.Frontiers in endocrinology · 2026Article
- Thyroiditis and human blood metabolites: A mendelian randomization study.Journal of medical biochemistry · 2025Article
- Circulating T cell atlas in Moyamoya disease: insights into immunopathogenesis of cerebrovascular disorders.Journal of neuroinflammation · 2025Article
- The interlink between thyroid autoimmunity and type 1 diabetes and the impact on male and female fertility.Hormones (Athens, Greece) · 2024Review
- A Flexible Mouse Model of Autoimmune Thyroiditis Induced by Immunization with an Adenovirus Containing Full-Length Thyroglobulin cDNA.Current protocols · 2024Article
- From Phenotype to Molecules: Unveiling the Genetic and Immunological Bridges Between Autoimmune Diseases and Vitiligo.Clinical, cosmetic and investigational dermatology · 2024Article
- Effective Inhibition of Thyroid Antigen Presentation Using Retro-Inverso Peptides in Experimental Autoimmune Thyroiditis: A Pathway Toward Immune Therapies of Thyroid Autoimmunity.Thyroid : official journal of the American Thyroid Association · 2023Article
- Genetics and epigenetics of autoimmune thyroid diseases: Translational implications.Best practice & research. Clinical endocrinology & metabolism · 2023Review
- Selective Silencing of Disease-Associated B Lymphocytes from Hashimoto's Thyroiditis Patients by Chimeric Protein Molecules.International journal of molecular sciences · 2022Article
- Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis.Brain : a journal of neurology · 2021Article
- An update on the pathogenesis of Hashimoto's thyroiditis.Journal of endocrinological investigation · 2021Review
- Type 1 Diabetes and Autoimmune Thyroid Disease-The Genetic Link.Frontiers in endocrinology · 2021Review
- Cepharanthine Blocks Presentation of Thyroid and Islet Peptides in a Novel Humanized Autoimmune Diabetes and Thyroiditis Mouse Model.Frontiers in immunology · 2021Article
- Identification of novel HLA-A0201-restricted T-cell epitopes against thyroid antigens in autoimmune thyroid diseases.Endocrine · 2020Article
- Bioinformatics analysis of key genes and pathways in Hashimoto thyroiditis tissues.Bioscience reports · 2020Article
- Primary DQ effect in the association between HLA and neurological syndromes with anti-GAD65 antibodies.Journal of neurology · 2020Article
- Cepharanthine blocks TSH receptor peptide presentation by HLA-DR3: Therapeutic implications to Graves' disease.Journal of autoimmunity · 2020Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Autoimmune polyglandular syndrome 3 variant (APS3v) refers to the co-occurrence of autoimmune thyroiditis (AITD) and type 1 diabetes (T1D) within the same individual. HLA class II confers the strongest susceptibility to APS3v. We previously identified a unique amino acid signature of the HLA-DR pocket (designated APS3v HLA-DR pocket) that predisposes to APS3v. We hypothesized that both thyroid and islet peptides can be presented by the unique APS3v HLA-DR pocket, triggering AITD + T1D together. To test this hypothesis we screened islet and thyroid peptides for their ability to bind to the APS3v HLA-DR pocket. Virtual screen of all possible thyroglobulin (Tg), thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), insulin (Ins), and glutamic acid decarboxylase 65 (GAD65) peptides identified 36 peptides that bound to this unique pocket. In vitro binding assays using baculovirus-produced recombinant APS3v HLA-DR identified 11 thyroid/islet peptides (of the 36 predicted binders) that bound with high affinity. By immunizing humanized HLA-DR3 mice carrying the APS3v HLA-DR pocket we identified 4 peptides (Tg.1571, GAD.492, TPO.758, TPO.338) that were presented by antigen presenting cells and elicited T-cell response. We conclude that both thyroid and islet peptides can bind to this flexible APS3v HLA-DR pocket and induce thyroid and islet specific T-cell responses. These findings set the stage to developing specific inhibitors of the APS3v HLA-DR pocket as a precision medicine approach to treating or preventing APS3v in patients that carry this genetic HLA-DR pocket variant.
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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.