Submit a Letter to the Editor for:
Takao Ando, Rauf Latif, Alla Pritsker, Thomas Moran, Yuji Nagayama, Terry F. Davies
J Clin Invest. 2002;
110(11):1667
doi:10.1172/JCI16991
Abstract |
Full text
|
PDF
T
he 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 α (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 α 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.
Guidelines:
The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. All accepted letters will be posted on our website within one week of acceptance. The Editors reserve the right to edit any letter for length, content, and clarity. Authors of all accepted letters will be asked to preview any changes. Authors will be notified by e-mail if their letters were not accepted. As this is a final decision, no appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML, if you wish. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editor directly at editors@the-jci.org.
