title: A monoclonal thyroid-stimulating antibody.
abstract: The thyrotropin receptor, also known as the thyroid-stimulating hormone receptor (TSHR), is the primary antigen of Graves disease. Stimulating TSHR antibodies are the cause of thyroid overstimulation and were originally called long-acting thyroid stimulators due to their prolonged action. Here we report the successful cloning and characterization of a monoclonal antibody (MS-1) with TSHR-stimulating activity. The thyroid-stimulating activity of MS-1 was evident at IgG concentrations as low as 20 ng/ml. MS-1 also competed for radiolabeled TSH binding to the native TSHR and was able to compete for TSH-induced stimulation. MS-1 recognized a conformational epitope within the TSHR alpha (or A) subunit but excluding the receptor cleavage region. Using an assay measuring loss of antibody recognition after cleavage we demonstrated that MS-1, in contrast to TSH, was unable to enhance TSHR posttranslational cleavage. Since receptor cleavage is followed by alpha subunit shedding and receptor degradation, the functional half-life of the receptor may be extended. The isolation and characterization of MS-1 provides a novel explanation for the prolonged thyroid stimulation in this disease which may be secondary to the lack of receptor cleavage in addition to the prolonged half-life of IgG itself.
authors.affiliation: Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA. takao.ando@mssm.edu
authors.forename: Takao
authors.initials: T
authors.lastname: Ando
authors.forename: Rauf
authors.initials: R
authors.lastname: Latif
authors.forename: Alla
authors.initials: A
authors.lastname: Pritsker
authors.forename: Thomas
authors.initials: T
authors.lastname: Moran
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagayama
authors.forename: Terry F
authors.initials: TF
authors.lastname: Davies
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D004195:Disease Models, Animal; D006111:Graves Disease / Q000276:immunology; D006801:Humans; D011989:Receptors, Thyrotropin / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D011989:Receptors, Thyrotropin; D011994:Recombinant Proteins