Abnormal Thyrotropin-Binding Immunoglobulins in Two Patients with Graves' Disease

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Abstract
Among 154 patients with Graves' disease, 2 patients with serum TSH-binding immunoglobulins (Igs) of high affinity were detected by the TSH binding inhibitor Ig (TBII) assay. These IgGs bound 60% and 83% of radioactively labeled TSH, respectively, as determined by polyethylene glycol precipitation, higher than the maximal specific binding (33%) in the TBII assay. Such binding was detected even in the absence of TSH receptors. The addition of bovine TSH (bTSH) or human TSH (hTSH) resulted in dose-dependent reduction in polyethylene glycol-precipitable radioactivity, though hTSH was much less effective. Further, TBII IgGs of high titer or myxedema sera with elevated serum TSH levels did not inhibit the reaction. Scatchard analysis using bTSH revealed that the IgG of 1 patient had a dissociation constant of 4.0 X 10−11 M and maximum specific binding of 1.6 x 10−14 M/mg IgG. The 7S fraction was found to be a major binding component by gel filtration chromatography, and immunoelectrophoresis and subsequent auto-radiography demonstrated the TSH-binding material to IgG with k-chain in both patients. Both of these patients possessed significant human thyroid stimulator activity and shared 6 of 8 loci in HLA studies. These patients are considered to have anti-TSH antibody, causing falsely increased binding of [125I]bTSH in the TBII assay. Such antibodies result in false TBII assay results and thus should be sought routinely in TBII assays.