ArticleThe Journal of clinical endocrinology and metabolism2015
Evidence that TSH Receptor A-Subunit Multimers, Not Monomers, Drive Antibody Affinity Maturation in Graves' Disease.
Article in The Journal of clinical endocrinology and metabolism, 2015. 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, 32 citations in OpenAlex.
- The thyrotropin receptor structure and interactions with autoantibodies.European thyroid journal · 2025Review
- Significance of pathological changes and chemokine expression in various organs in a Graves' disease animal model.Journal of molecular histology · 2025Article
- Expression, immunogenicity and clinical significance analysis of thyroid‑stimulating hormone receptor fusion proteins.Molecular medicine reports · 2025Article
- Monoclonal Antibodies to Thyrotropin Receptor With Thyroid-Stimulating Activity Activate the NF-κB Pathway to Induce Chemokine Expression.Journal of cellular and molecular medicine · 2025Article
- Exploring antigenic variation in autoimmune endocrinopathy.Frontiers in immunology · 2025Review
- Graves disease: latest understanding of pathogenesis and treatment options.Nature reviews. Endocrinology · 2024Review
- 2021 update on thyroid-associated ophthalmopathy.Journal of endocrinological investigation · 2022Review
- New Therapeutic Horizons for Graves' Hyperthyroidism.Endocrine reviews · 2020Review
- Graves' disease.Nature reviews. Disease primers · 2020Review
- Review
- High-level intrathymic thyrotrophin receptor expression in thyroiditis-prone mice protects against the spontaneous generation of pathogenic thyrotrophin receptor autoantibodies.Clinical and experimental immunology · 2017Article
- TSHR as a therapeutic target in Graves' disease.Expert opinion on therapeutic targets · 2017Review
- Structural-Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work.Frontiers in endocrinology · 2017Review
- Critical Differences between Induced and Spontaneous Mouse Models of Graves' Disease with Implications for Antigen-Specific Immunotherapy in Humans.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- TSH Receptor Cleavage Into Subunits and Shedding of the A-Subunit; A Molecular and Clinical Perspective.Endocrine reviews · 2016Review
- Withdrawn: TSH Receptor Cleavage Into Subunits and Shedding of the A-Subunit; A Molecular and Clinical Perspective.Endocrine reviews · 2016Review
- Thyrotropin Receptor Epitope and Human Leukocyte Antigen in Graves' Disease.Frontiers in endocrinology · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
contextThe TSH receptor (TSHR) A-subunit shed from the cell surface contributes to the induction and/or affinity maturation of pathogenic TSHR autoantibodies in Graves' disease.
objectiveThis study aimed to determine whether the quaternary structure (multimerization) of shed A-subunits influences pathogenic TSHR autoantibody generation.
designThe isolated TSHR A-subunit generated by transfected mammalian cells exists in two forms; one (active) is recognized only by Graves' TSHR autoantibodies, the second (inactive) is recognized only by mouse monoclonal antibody (mAb) 3BD10. Recent evidence suggests that both Graves' TSHR autoantibodies and mAb 3BD10 recognize the A-subunit monomer. Therefore, if the A-subunit monomer is an immunogen, Graves' sera should have antibodies to both active and inactive A-subunits. Conversely, restriction of TSHR autoantibodies to active A-subunits would be evidence of a role for shed A-subunit multimers, not monomers, in the pathogenesis of Graves' disease. Therefore, we tested a panel of Graves' sera for their relative recognition of active and inactive A-subunits.
resultsOf 34 sera from unselected Graves' patients, 28 were unequivocally positive in a clinical TSH binding inhibition assay. None of the latter sera, as well as 8/9 sera from control individuals, recognized inactive A-subunits on ELISA. In contrast to Graves' sera, antibodies induced in mice, not by shedding from the TSHR holoreceptor, but by immunization with adenovirus expressing the free human A-subunit, were directed to both the active and inactive A-subunit forms.
conclusionsThe present study supports the concept that pathogenic TSHR autoantibody affinity maturation in Graves' disease is driven by A-subunit multimers, not monomers.
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