Implications of new monoclonal antibodies and the crystal structure of the TSH receptor for the treatment and management of thyroid diseases

Autoantibodies to the thyroid-stimulating hormone receptor (TSHR) cause the hyperthyroidism of Graves ’ disease and contribute to Graves ’ eye signs. Human monoclonal TSHR autoantibodies prepared from patients ’ lymphocytes have important clinical applications in terms of their ability to stimulate...

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Vydáno v:Biomarkers in medicine Ročník 2; číslo 6; s. 567 - 576
Hlavní autoři: Rees Smith, Bernard, Sanders, Jane, Furmaniak, Jadwiga
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Future Medicine Ltd 01.12.2008
Témata:
Autoantibodies
Autoimmunity
Binding sites
Cancer
Care and treatment
Crystals
Disease
Eye diseases
Graves ’ disease
Hormones
Hypothyroidism
Immune system
Inventors
Lymphocytes
Molecular weight
Monoclonal antibodies
Proteins
Structure
thyroid
Thyroid diseases
Thyroid gland
thyroid-stimulating hormone
Thyrotropin
TSH
TSH receptor
ISSN:1752-0363, 1752-0371, 1752-0371
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Shrnutí:Autoantibodies to the thyroid-stimulating hormone receptor (TSHR) cause the hyperthyroidism of Graves ’ disease and contribute to Graves ’ eye signs. Human monoclonal TSHR autoantibodies prepared from patients ’ lymphocytes have important clinical applications in terms of their ability to stimulate TSHR-containing tissues. Also, TSHR monoclonal antibodies that act as antagonists may well be useful in treating Graves ’ eye disease. Recently, the high-resolution (2.55 ÅÅ) crystal structure of the TSHR in complex with a monoclonal thyroid-stimulating autoantibody has been determined, and this provides key insights into how the autoantibodies interact with the receptor. Furthermore, the structure can be used in the rational design of small molecules that will disrupt receptor binding by thyroid-stimulating autoantibodies, thus providing new strategies to control TSHR activation in addition to monoclonal antibodies.
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ISSN:1752-0363
1752-0371
1752-0371
DOI:10.2217/17520363.2.6.567