The background of the study. Hyperthyroidism in Graves' disease is caused by antibodies to the thyrotropin (TSH) receptor on thyroid cells that stimulate the function of the cells in the same way as does TSH. For years, the only source of these antibodies was the serum of patients with Graves' hyperthyroidism. In this study, basic immunologic techniques were used to produce antibodies to the TSH receptor from single clones of mouse cells.
How the study was done. Mice were immunized with DNA complementary to the DNA that codes for the receptor for TSH present on thyroid cells. Spleen cells from mice that produced the most antibodies to the TSH receptor were cultured in vitro and cloned, and three monoclonal antibodies were isolated. These antibodies were tested for their ability to inhibit the binding of TSH to TSH receptors and to mimic the action of TSH on thyroid cells. The ability of serum from patients with Graves' hyperthyroidism and normal subjects to block the binding of the mouse antibodies also was studied.
The results of the study. The three mouse antibodies inhibited the binding of TSH to TSH receptors and stimulated the function of thyroid cells. Serum from patients with Graves' hyperthyroidism blocked the binding of both mouse antibodies and TSH to TSH receptors with approximately equal potency, whereas serum from normal subjects did not.
The conclusions of the study. Monoclonal antibodies against the TSH receptor have properties similar to the TSH-receptor antibodies found in the serum of patients with Graves' hyperthyroidism.
The original article. Sanders J, Jeffreys J, Depraetere H, Richards T, Evans M, Kiddie A, Brereton K, Groenen M, Oda Y, Furmaniak J, Rees Smith B. Thyroid-stimulating monoclonal antibodies. Thyroid 2002;12:1043-50