A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves' disease

Watson, P.; Ajjan, Ramzi; Phipps, Jacqueline; Metcalfe, Russell; Weetman, Anthony P.

doi:10.1046/j.1365-2265.1998.00619.x

Cited by 50 publications

(27 citation statements)

References 21 publications

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“…In recent years, human thyroid cell assays have been replaced by Chinese hamster ovary (CHO) cells expressing the rhTSHR (20). In some assays, cAMP is indirectly detected by means of a light-generating reporter molecule (21). Since both TSH-blocking antibodies (TBAb) and TSAb will be positive in the TBI assay, only the bioassay can be used to specifically detect the former type of autoantibody.…”

Section: Tbab Tsab and Switching Between Hypo-and Hyperthyroidismmentioning

confidence: 99%

Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa

McLachlan

Rapoport

2013

Thyroid

196

169

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Section: Tbab Tsab and Switching Between Hypo-and Hyperthyroidismmentioning

confidence: 99%

Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa

McLachlan

Rapoport

2013

Thyroid

196

169

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“…At present, the only method for detecting TSH-R stimulating antibodies remains bioassay, with all the vagaries that this imposes, coupled with low and slow throughput. To screen large numbers of potentially stimulating antibodies, new assay methods have been developed including a cell line transfected with the TSH-R coupled to a cyclic AMP-luciferase signalling system, allowing rapid read-out of cyclic AMP production in a luminometer (66). Others have developed transfected cell lines with the TSH-R expressed on the cell via a glycosylphosphatidylinositol (GPI) anchor; high levels of surface receptor allow these cells to be used in sensitive flow cytometry assays (67,68).…”

Section: Tpo and Tsh-r Autoantibodiesmentioning

confidence: 99%

Autoimmune thyroid disease: propagation and progression

Weetman

2003

European Journal of Endocrinology

207

146

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Autoimmune thyroid disease is the archetype for organ-specific autoimmune disorders. Progress in treating these disorders lies in improvements of our understanding of the predisposing factors responsible, the mechanisms responsible for progression of disease, and the interaction between thyroid antigens and the immune system at the level of the T cell and antibody. In common with other autoimmune diseases, genetic, environmental and endogenous factors are required in an appropriate combination to initiate thyroid autoimmunity. At present the only genetic factors which have been confirmed lie in the HLA complex and CTLA-4 or a closely linked gene. Identifying other predisposing genes will require large-scale family studies, or further insights into likely candidate genes. A number of environmental factors are known to predispose to autoimmune thyroid disease, including smoking, stress and iodine intake, while immunomodulatory treatments are revealing new pathways for disease emergence. The thyroid cell itself appears to play a major role in disease progression, interacting with the immune system through expression of a number of immunologically active molecules including HLA class I and II, adhesion molecules, cytokines, CD40 and complement regulatory proteins. New techniques, in particular phage display libraries, are providing the methods with which to identify autoantibody diversity in autoimmune thyroid disease and to provide tools for mapping autoantigenic epitopes. Application of these techniques is likely to lead to an understanding of how TSH receptor antibodies interact with the receptor to cause Graves' disease and also to the identification of novel orbital autoantigens in thyroid-associated ophthalmopathy.

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“…Most commonly these assays rely on the determination of intracellular cAMP accumulation. More recent developments include measurement of cAMP-dependent luciferase reporter gene activity [93,94]. The TSH receptor epitopes for TSAb and TBAb are not well defined [9,14,17].…”

Section: Graves' Diseasementioning

confidence: 99%

Human Genome and Diseases: Review¶The TSH receptor and its role in thyroid disease

Kopp

2001

CMLS, Cell. Mol. Life Sci.

123

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The thyrotropin (TSH) receptor plays a preeminent role in thyroid physiology and disease. TSH, acting through the TSH receptor, is the major stimulator of thyroid cell growth, differentiation and function. In Graves' disease, the TSH receptor is the target of stimulating antibodies that cause hyperthyroidism. Although still a topic of debate, the TSH receptor has been implicated in the pathogenesis of the endocrine ophthalmopathy associated with Graves' disease. Blocking antibodies against the TSH receptor are involved in the development of hypothyroidism in a subset of patients with autoimmune hypothyroidism. Transplacental passage of stimulating or blocking TSH receptor antibodies from a mother with autoimmune thyroid disease may result in transient hyper- or hypothyroidism in early infancy. During pregnancy, the placental hormone human choriogonadotropin (hCG) can cause gestational hyperthyroidism through cross-reaction with the TSH receptor. Gestational hyperthyroidism may also be involved in the pathogenesis of hyperemesis gravidarum. Trophoblast tumors secreting hCG are a rare cause of hyperthyroidism. Somatic activating mutations of the TSH receptor have been identified as a molecular cause of toxic adenomas, whereas activating mutations in the germline give rise to nonautoimmune familial hyperthyroidism or sporadic congenital hyperthyroidism. These gain-of-function mutations are dominant, and one mutated allele is sufficient to result in disease. Inactivating germline mutations of both TSH receptor alleles lead to variable degrees of resistance to TSH, encompassing a spectrum ranging from euthyroid hyperthyrotropinemia to overt hypothyroidism with thyroid hypoplasia.

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A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves' disease

Abstract: The present report describes a simple, sensitive and rapid assay for the detection of TSAb, with application both in the clinical analysis of GD patient sera and as a potential research tool for use in the isolation of TSAb monoclonal antibodies.

Cited by 50 publications

References 21 publications

Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa

Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa

Autoimmune thyroid disease: propagation and progression

Human Genome and Diseases: Review¶The TSH receptor and its role in thyroid disease

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