Performance and Specificity of 6 Immunoassays for TSH Receptor Antibodies: A Multicenter Study

Diana, Tanja; Wüster, Christian; Olivo, Paul D.; Unterrainer, Angelica; König, Jochem; Kanitz, Michael; Bossowski, Artur; Decallonne, Brigitte; Kahaly, George J.

doi:10.1159/000478522

Cited by 58 publications

(36 citation statements)

References 26 publications

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“…A meta-analysis of 21 studies showed that the overall pooled sensitivity and specificity of the serum TSH-R-Ab concentration measured with second-and third-generation binding assays were 97 and 98%, respectively [25]. In contrast, the highly sensitive cell-based bioassays [26][27][28][29][30][31][32][33] exclusively differentiate between the TSH-R-stimulating Ab (TSAb) and TSH-R-blocking Ab [34,35]. Also, TSAb is a highly sensitive and predictive biomarker for the extrathyroidal manifestations of GD [36][37][38][39][40][41][42] as well as a useful predictive measure of fetal or neonatal hyperthyroidism [43,44].…”

Section: Serologymentioning

confidence: 99%

2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

Kahaly¹,

Bartalena²,

Hegedüs³

et al. 2018

Eur Thyroid J

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Graves’ disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves’ hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves’ hyperthyroidism are usually medically treated for 12–18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12–18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves’ patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves’ patients with mild/active orbitopathy receiving RAI.

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Section: Serologymentioning

confidence: 99%

2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

Kahaly¹,

Bartalena²,

Hegedüs³

et al. 2018

Eur Thyroid J

Self Cite

678

650

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“…Finally, the chimeric TSHR used in the commercial bioassay and bridge assay are 'seen' by some TBAb [16,24]. TBAb can reduce the stimulatory effect of TSAb in vitro [21,25] as well as in vivo [26]. Therefore, even a bioassay (whether using a chimeric or wild-type TSHR) whose 'readout' is a signal for TSHR activation rather than ligand binding is not immune from interference by TBAb, if present in the same serum.…”

Section: A) Tshr Autoantibody Assaysmentioning

confidence: 99%

Reflections on Thyroid Autoimmunity: A Personal Overview from the Past into the Future

Rapoport

McLachlan

2018

Horm Metab Res

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After investigating thyroid autoimmunity for more than 40 years, we present a personal perspective on the field. Despite effective therapies for Graves’ hyperthyroidism and Hashimoto’s thyroiditis, cures are elusive. Novel forms of therapy are being developed, such as small molecule inhibitors of the TSH receptor (TSHR), but cure will require immunotherapy. This goal requires advances in understanding the pathogenesis of thyroid autoimmunity, the ‘keys’ for which are the thyroid antigens themselves. Presently, however, greater investigative focus is on non-thyroid specific immune cell types and molecules. Thyroid autoantigens are the drivers of the autoimmune response, a prime example being the TSHR. In our view, the TSHR is the culprit as well as the victim in Graves’ disease because of its unique structure. Unlike the closely related gonadotropin receptors, the TSHR cleaves into subunits and there is strong evidence that its shed extracellular A-subunit, not the holoreceptor, is the major antigen driving pathogenic thyroid stimulating autoantibodies (TSAb) development. There is no Graves’ disease of the gonads. Studies of potential antigen-specific immunotherapies require an animal model. Such models have been developed in which TSAb can be induced or, more importantly, arise spontaneously. Not appreciated until recently by thyroid investigators is that B cell surface autoantibodies are highly efficient ‘antigen receptors’ and the epitope to which an autoantibody binds influences antigen processing and which peptide is presented to T cells. These animal models and recombinant human autoantibodies cloned from Graves’ and Hashimoto’s B cells (plasma cells) are available for study by future generations.

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“…Current third‐generation assays are highly sensitive and specific for TRAb and are an excellent tool in both GD diagnosis and the characterization of extrathyroidal features of GD . However, receptor binding assays are currently unable to distinguish between thyroid‐stimulating antibodies (TSAb) and thyroid‐stimulating blocking (TSBAb) antibodies . Instead, bioassays measuring the cAMP response to TRAb stimulation, or inhibition of TSH induced stimulation of TSH receptor (TSHR) using cells expressing the TSHR, remain an invaluable tool for differentiation between TSAb and TSBAb.…”

Section: Introductionmentioning

confidence: 99%

“…thyroid-stimulating antibodies (TSAb) and thyroid-stimulating blocking (TSBAb) antibodies. 5 Instead, bioassays measuring the cAMP response to TRAb stimulation, or inhibition of TSH induced stimulation of TSH receptor (TSHR) using cells expressing the TSHR, remain an invaluable tool for differentiation between TSAb and TSBAb. Subjects with autoimmune thyroid disease (AITD) can have a mixture of TSAb and TSBAb, [6][7][8][9] and their clinical presentation depends in part on whether TSAb or TSBAb activity is predominant.…”

mentioning

confidence: 99%

Thyrotrophin receptor antibody concentration and activity, several years after treatment for Graves’ disease

Nalla

Young

Sanders

et al. 2018

Clinical Endocrinology

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Summary Objective TSH receptor antibodies (TRAb) are responsible for autoimmune hyperthyroid disease (Graves’ disease; GD) with TRAb levels tending to decrease following treatment. Measurement of TRAb activity during follow‐up could prove valuable to better understand treatment effectiveness. Study design TRAb concentration and stimulating (TSAb) and blocking (TSBAb) activity of patient serum were assessed following different treatment modalities and follow‐up length. Methods Sixty‐six subjects were recruited following treatment with carbimazole (n = 26), radioiodine (n = 27) or surgery (n = 13). TRAb, TPOAb, TgAb and GADAb were measured at a follow‐up visit as well as bioassays of TSAb and TSBAb activity. Results Forty‐five per cent of all patients remained TRAb‐positive for more than one year and 23% for more than 5 years after diagnosis, irrespective of treatment method. Overall, TRAb concentration fell from a median (IQR) of 6.25 (3.9‐12.7) to 0.65 (0.38‐3.2) U/L. Surgery conferred the largest fall in TRAb concentration from 11.4 (6.7‐29) to 0.58 (0.4‐1.4) U/L. Seventy per cent of TRAb‐positive patients were positive for TSAb, and one patient (3%) was positive for TSBAb. TRAb and TSAb correlated well (r = 0.83). In addition, 38/66 patients were TgAb‐positive, 47/66 were TPOAb‐positive and 6/66 were GADAb‐positive at follow‐up. Conclusions TRAb levels generally decreased after treatment but persisted for over 5 years in some patients. TRAb activity was predominantly stimulatory, with only one patient demonstrating TSBAb. A large proportion of patients were TgAb/TPOAb‐positive at follow‐up. All treatment modalities reduced TRAb concentrations; however, surgery was most effective.

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Performance and Specificity of 6 Immunoassays for TSH Receptor Antibodies: A Multicenter Study

Cited by 58 publications

References 26 publications

2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

Reflections on Thyroid Autoimmunity: A Personal Overview from the Past into the Future

Thyrotrophin receptor antibody concentration and activity, several years after treatment for Graves’ disease

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