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Evidence Against the Importance in the Disease Process of Antibodies to Bovine Thyroid-Stimulating Hormone Found in Some Patients With Graves' Disease

Ito Hospital, 4-3-6 Jingumae, Shibuya-ku Tokyo 150, Japan
the Second Department of Internal Medicine, Osaka City University Medical School (N.H., H.M.) 1-5-7 Asahimachi, Abeno-ku, Osaka 545, Japan

Address all correspondence and requests for reprints to: Kunihiko Ito, M.D., Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo 150, Japan.

The antibody to TSH (TSH-Ab) found in some patients with Graves' disease may be either an antiidiotype (antiid- Ab) to the TSH receptor antibody (TRAb) or the antigen (idiotype) for which the anti-id-Ab is in fact TRAb. Four groups have found antibodies to bovine TSH (bTSH-Ab) in Graves' disease patients in a TSH binding-inhibiting immunoglobulin (TBII) RRA that uses [¹²⁵I]bTSH. In this assay serum samples containing bTSH-Ab give highly negative TBII values. The purpose of this study was to look for any clinical significance of potential idiotypic-antiidiotypic network regulation related to bTSH-Ab. Twenty-one (0.49%) of 4285 Graves' disease patients had TBII values less than the mean – 4 SD of normal subjects. In all 21, bTSH-Ab was found by incubation of [¹²⁵I]bTSH with the patient's serum, and significant inhibition of binding of bTSH-Ab to bTSH by human TSH was found in only 3 of these serum samples.

We investigated next whether the binding site of the anti- TSH-Ab mimicked the TSH receptor-binding site. Binding of[¹²⁵I]bTSH to bTSH-Ab-positive serum was notinhibited by bTSH-Ab-negative, thyroid-stimulating immunoglobulin-positive [(+)], and/or TBII(+) immunoglobulin G. In one patient with human TSH-Ab, TSH-Ab appeared and disappeared, and when TSH-Ab was negative, TBII was positive. Inhibition of [¹²⁵I]bTSH binding to TSH-Ab by the same patient's serum when that patient was serum thyroid-stimulating immunoglobulin(+), TBII(+), and TSH-Ab-negative was sought but not found. Changes in serum TSH-Ab activity and disease activity were not correlated in this patient. In six untreated patients with Graves' hyperthyroidism with bTSH-Ab, the serum T₃ and T₄ concentrations and the time required to become euthyroid during antithyroid drug treatment were not significantly different from those in 52 such patients without bTSH-Ab. These data suggest that bTSH-Ab is not an anti-id-Ab to TRAb and that TSH-Ab does not directly modulate the activity of Graves' disease.

Received March 21, 1988.

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