Bioassay Projekt
Laufzeit: 01.01.2015 - 31.12.2021
Kurzfassung
Autoantibodies (Ab) to the thyroid stimulating hormone receptor (TSHR) are responsible for several clinical manifestations of autoimmune thyroid diseases (AITD) and are specific biomarkers of these autoimmune endocrine disorders. Graves’ disease (GD) is characterized by the production of autoantibodies to thyroid-associated antigens such as the thyrotropin receptor (TSHR). The pathophysiology of the hyperthyroidism of GD is related to thyroid-stimulating antibodies (TSAb) that activate the...Autoantibodies (Ab) to the thyroid stimulating hormone receptor (TSHR) are responsible for several clinical manifestations of autoimmune thyroid diseases (AITD) and are specific biomarkers of these autoimmune endocrine disorders. Graves’ disease (GD) is characterized by the production of autoantibodies to thyroid-associated antigens such as the thyrotropin receptor (TSHR). The pathophysiology of the hyperthyroidism of GD is related to thyroid-stimulating antibodies (TSAb) that activate the TSHR on thyroid follicular cells, leading to unregulated thyroid hormone production. These functional autoantibodies mimic the receptor’s natural ligand by stimulating cyclic adenosine monophosphate (cAMP)-dependent signal transduction, but other anti-TSHR antibodies antagonize the TSHR by either blocking TSH binding (TBAb) or interacting with TSHR epitopes that inhibit cAMP production. These Ab can be measured either via competitive-binding immunoassays or with cell-based bioassays.
Functional TSHR Ab bioassays distinguish between TSHR-stimulating and blocking Ab through their effect on cyclic adenosine monophosphate production in a cell line stably transfected with a chimeric human receptor. Bioassays for TSHR-stimulating and blocking Ab are routinely performed in our research lab.
Aims of the bioassay project are to develop and validate second generation functional bioassays for the measurement of stimulating and blocking TSHR Ab. Subsequently, standardization of these bioassays with international reference material is foreseen. Further aims are to investigate the functionality of TSHR-Abs and small molecule, "drug-like" TSHR agonists and antagonists. The increase of cAMP levels versus luciferase gene activity will be investigated in different cell lines after incubation with serum from patients with AITD.» weiterlesen» einklappen
Veröffentlichungen
- Kiefer, Florian W.; Klebermass-Schrehof, Katrin; Steiner, Manuel et al.
- Fetal/Neonatal Thyrotoxicosis in a Newborn From a Hypothyroid Woman With Hashimoto Thyroiditis
- Diana, Tanja; Wuester, Christian; Olivo, Paul D. et al.
- Performance and Specificity of 6 Immunoassays for TSH Receptor Antibodies: A Multicenter Study
- Diana, T.; Krause, J.; Olivo, P. D. et al.
- Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease
- Kahaly, George J.; Diana, Tanja
- TSH Receptor Antibody Functionality and Nomenclature
- Diana, Tanja; Li, Yunsheng; Olivo, Paul D. et al.
- Analytical Performance and Validation of a Bioassay for Thyroid-Blocking Antibodies
- Bossowski, Artur; Moniuszko, Marcin; Idzkowska, Ewelina et al.
- Decreased proportions of CD4+IL17+/CD4+CD25+CD127-and CD4+IL17+/CD4+CD25+CD127-FoxP3+T cells in children with autoimmune thyroid diseases
- Diana, T.; Wuester, C.; Kanitz, M. et al.
- Highly variable sensitivity of five binding and two bio-assays for TSH-receptor antibodies
- Kahaly, George J.; Diana, Tanja; Glang, Jennifer et al.
- Thyroid Stimulating Antibodies Are Highly Prevalent in Hashimoto's Thyroiditis and Associated Orbitopathy
