THYROID-STIMULATING ANTIBODIES IN GRAVES-DISEASE AND THE EFFECT OF THYROTROPHIN-BINDING GLOBULINS ON THEIR DETERMINATION

Globulin preparations from the sera of 104 untreated patients with Grave''s disease have been tested for their thyroid-stimulating antibody (TSAb) activities. Of the samples (81), (78%) were positive in the assay for the TSH-binding inhibitory Ig, 48 samples (46%) contained human thyroid adenylate cyclase stimulators (HTACS) and 71 (68%) contained human thyroid stimulators (HTS) measured as stimulation of colloid droplet formation in human thyroid slices. All 104 samples were positive in 1 or other of the assays, 29 (28%) were positive in all 3 assays and 38 (37%) in 2. All samples were tested for their specific TSH-binding characteristics, 40 (38%) possessed B-type binding sites (previously characterized as TSH-binding sites with low affinity but high capacity for the ligand); the remaining 64 samples (62%) were no different from normal control samples and had A-type binding sites (high affinity but low capacity binding sites for TSH). Samples without detectable TSH-binding inhibitory Ig did not contain B-type TSH-binding globulins. Globulins exhibiting B-type binding were more active in the HTACS and HTS assays. The B-type TSH-binding globulins have a characteristic, dose-dependent reducing effect on the human thyroid adenylate cyclase stimulation by TSH; A-type globulins do not. Globulins exhibiting B-type TSH-binding may therefore have a significant effect on assays for TSAb activities. The methods used to measure TSAb have been reviewed from this point of view.