Production of mouse antibodies that act
like the thyroid-stimulating antibodies of Graves' disease
(March 2003)
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
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