ANTI‐TSH ANTIBODY WITH HIGH SPECIFICITY TO HUMAN TSH IN SERA FROM A PATIENT WITH GRAVES' DISEASE: ITS ISOLATION FROM, AND INTERACTION WITH, TSH RECEPTOR ANTIBODIES

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Abstract
A patient with thyrotoxic Graves' disease had an apparent measurable level of serum TSH (2–5 μU/ml) by double‐antibody radioimmunoassay (RIA). The serum IgG bound with both [125I]human(h)TSH and [125I]bovine(b)TSH. The [125I]hTSH binding was more effectively displaced by human than bovine TSH, whereas [125I]bTSH binding was displaced exclusively by bTSH. Scatchard analyses revealed that [125I]hTSH binding showed two components, whereas [125I]bTSH binding had only one component. Serum TSH determined by RIA became undetectable 21 months after antithyroid drug treatment with a parallel decrease of [125I]hTSH binding IgG activity. Four thyrotrophin binding inhibitory immunoglobulins (TBII) from other patients did not interfere with the binding of the patient's serum to [125I]h‐ or bTSH. Furthermore, the in‐vitro thyroid stimulating activities of three thyroid stimulating antibodies (TSAb) were not affected by the addition of this patient's IgG. On the other hand, this patient's Ig (3 mg/ml) abolished the in‐vitro thyroid stimulation by bTSH (100 /μU/ml), but did not affect that by hTSH (100 /μU/ml). The anti‐hTSH antibody, TSH receptor antibody and anti‐bTSH antibody in the serum, which contains TSAb as well as anti‐TSH antibodies, could be partially purified by hTSH‐agarose and subsequently by guinea pig fat cell membrane affinity absorptions. However, the anti‐hTSH antibody fraction obtained had both hTSH binding activity and thyroid stimulating activity, and this fraction did not show any inhibitory effect on the in‐vitro thyroid stimulation of autologous TSH receptor antibody or hTSH. The possible significance of anti‐TSH antibodies is discussed.

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