TSH-displacing activity versus TSH-binding inhibiting activity of immunoglobulins from patients with Graves’ disease

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Abstract
Inhibition of binding of TSH to thyroid plasma membranes by immunoglobulins G (IgG) from patients with Graves’ disease has been interpreted as evidence of an interaction with the TSH receptor, but other explanations may account for this phenomenon. Displacement of receptor-bound TSH might be a more direct index of such an interaction. The aim of the present study was to assess TSH-displacing activity (TDA) of Graves’ IgG by a newly developed assay and compare TDA to TSH-binding inhibiting activity (TBIA) and thyroid-stimulating antibody (TSAb) activity. TDA was assessed by preincubating 125I-TSH with thyroid plasma membranes and by measuring residual bound 125I-TSH after addition of IgG. TBIA was evaluated by determining binding of 125I-TSH to thyroid plasma membranes preincubated with IgG. Results were expressed as % TSH-displacing or binding inhibition activities of test IgG with respect to normal control IgG. The percent of TDA positive Graves’ IgG preparations (72.7%) was greater than that of TBIA positive (48.5%). There was no correlation between TDA and TBIA results, since 11 Graves’ IgG preparations were TDA positive but TBIA negative, and 6 were TDA negative but TBIA positive. Hashimoto’s or idiopatic myxedema IgG preparations were positive in 2/7 in the TDA and in 1/7 in the TBIA assays, respectively. Neither TDA nor TBIA correlated with TSAb determined by cAMP accumulation in thyroid plasma membrane. The TDA assay developed in this study appeared to be more sensitive than the more widely used TBIA assay. No correlation was found between the two assays, indicating that inhibition of TSH binding and displacement of bound TSH are not equivalent and may be due to different phenomena. TDA as well as TBIA were also unrelated to TSAb activity, suggesting that interaction with the TSH receptor does not necessarily imply stimulation of thyroid function.

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