Heterogeneity of Graves' immunoglobulin G: comparison of thyrotropin receptor antibodies in serum and in culture supernatants of lymphocytes transformed by Epstein-Barr virus infection.

It is well known that in patients with Graves' disease there is dissociation among values for TSH receptor antibodies such as TSH binding-inhibiting antibody (TBIAb) and thyroid-stimulating antibody (TSAb). This study was designed to compare TSH receptor antibodies in serum and in culture supernatants of lymphocytes transformed by Epstein-Barr virus (EBV) infection. TBIAb was assayed using solubilized porcine thyroid membranes and TSAb using cultured porcine thyroid cells. Transformation of peripheral lymphocytes by EBV was performed in eight untreated hyperthyroid patients with Graves' disease who had a clear dissociation between values for TBIAb and TSAb, even after multiple dilutions of serum. EBV-infected lymphocytes from a patient were distributed into the wells of 4 24-well culture plates. After the first 4-week culture, the cells in each well positive for TBIAb and/or TSAb were further distributed to 12 wells and cultured for 2 weeks. In the supernatants of 372 wells of the second culture in the 8 patients, 31 were positive for TBIAb, and 41 were positive for TSAb. Among the 76 wells positive for TSH receptor antibodies, 72 wells (94.7%) were positive in only 1 assay. These results suggest that there are two types of TSH receptor antibodies, one having a single function (TBIAb or TSAb) and the other multifunctional (both), in Graves' patients. The incidence of the single functional type is much greater than that of the multifunctional type. We conclude, therefore, that the heterogeneity of Graves' immunoglobulin G is due mainly to multiple antibodies with a single function.