rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2002-12-4
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-10383466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-10448087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-10528222,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-11160239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-11201849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-11535591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-11884447,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-11917095,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-11923470,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-12122107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-1570295,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-1733738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-3286231,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-6292912,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-7864905,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-8094393,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-8496155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-8626810,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-8753787,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-8784060,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-8855311,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-9024244,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-9202233,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-9398703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-9442031,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-9570567,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-9737366,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-9861544,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12464672-9867816
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9738
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
110
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1667-74
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:12464672-Animals,
pubmed-meshheading:12464672-Antibodies, Monoclonal,
pubmed-meshheading:12464672-CHO Cells,
pubmed-meshheading:12464672-Cricetinae,
pubmed-meshheading:12464672-Disease Models, Animal,
pubmed-meshheading:12464672-Graves Disease,
pubmed-meshheading:12464672-Humans,
pubmed-meshheading:12464672-Receptors, Thyrotropin,
pubmed-meshheading:12464672-Recombinant Proteins
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pubmed:year |
2002
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pubmed:articleTitle |
A monoclonal thyroid-stimulating antibody.
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pubmed: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
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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