Interactions between TSH binding inhibiting--and adenylate cyclase stimulating--antibodies in Graves' disease

It is well known that there exists a dissociation between TSH binding inhibiting antibody (TBIAb) and thyroid stimulating antibody (TSAb) in some patients with Graves' disease. The present studies were undertaken to investigate the interaction between TBIAb and TSAb quantitatively using porcine thyroid cells in order to determine whether the binding sites of TBIAb and TSAb are identical or independent from each other. TBIAb was determined using solubilized porcine thyroid membrane and TSAb using cultured porcine thyroid cells, and both were expressed as equivalent amounts of bovine TSH. In order to avoid interassay variations, all determinations were performed with a single batch of porcine thyroids. Serum samples were obtained from ten untreated patients with Graves' disease; two were negative for TBIAb and TSAb, two were TBIAb negative and TSAb positive, two were weak positive for both, two were strong positive for both, and two were TBIAb strong and TSAb weak positive. IgG from each patient were mixed with equal amounts of IgG of the other nine patients. In order to observe interactions, measured values for TBIAb and TSAb of mixed samples were compared to estimated values (addition of values of original samples). The correlation coefficient between measured values and estimated values for TBIAb was +0.964, and that for TSAb was +0.989. These results that TBIAb does not interfere with the activity of TSAb and vice versa suggest that at least in some patients with Graves' disease, TBIAb and TSAb are different antibodies which have different binding sites.