Abstract
Using the TSH binding inhibition IgG (TBII) assay three patients with Graves’ disease were discovered to have serum TSH-binding immunoglobulins of high affinity. These IgGs bound 61%, 33% and 60% of radiolabeled TSH, respectively, higher than the maximal specific binding (25%) in the TBII assay. Such binding was detected even in the absence of TSH receptor with only small differences in the precipitable radioactivity (61 %, 28%, and 61 %, respectively) compared with non-specific binding (11.3%). The (125)I-bTSH binding of IgGs was competitively inhibited by the addition of bTSH. The 7s fraction was found to be a major binding component by gel filtration chromatography. Myxedema sera with high TSH levels did not affect the reaction. Moreover IgG binding to bTSH was not inhibited by the addition of serial dilutions of TBII positive pooled Graves’ IgG (0.1–10mg/ml) from a different untreated patient. The titers of these TSH binding antibodies were not changed during the treatment of Graves’ disease. Following guinea pig fat cell membrane receptor purification, the IgG of one patient with Graves’ disease revealed TBII activity of 46.3%. However, no binding of (125)I-bTSH in the absence of the TSH receptor was evident. These studies suggest that 1) anti-TSH antibodies and TSH receptor antibodies are present independent of one another in the sera of some patients with Graves’ disease, and 2) TSH receptor antibodies do not affect the binding of anti-TSH antibodies to TSH.