Thyrotropin Receptor Autoantibodies Recognizing Two Different Epitopes on the TSH Receptor: Lack of Relationship to Patient Age,Sex,and Ophthalmopathy

The existence of two populations of stimulatory TSH receptor autoantibodies against different epitopes raises the possibility of a link between one type of autoantibody and the clinical manifestations of Graves' disease. To test this hypothesis, serum immunoglobulins from 48 patients with Graves' disease were assayed for TSH binding inhibition (TBI) activity with two different recombinant TSH receptor variants (TSH-LHR-6 and TSH-LHR-6-A1) expressed on Chinese hamster ovary cells. The activity of 27 of the 48 patients' immunoglobulin samples was significantly less (difference in TBI value of 9% or greater) with chimera 6-A1 than with chimera 6. No immunoglobulin sample had significantly greater TSH binding inhibitory activity with chimera 6-A1 than with chimera 6. Sensitivity to the 6-A1 epitope substitution did not correlate with patient age, sex, or the presence or absence of hyperthyroidism. Further, there was no segregation of individual patients with TSH receptor autoantibodies with 6-A1 epitope sensitivity in terms of the past or present occurrence of ophthalmopathy, including the severity (total eye score), clinical activity, duration, and type of therapy. These data indicate that recognition by autoantibodies of the 6-A1 epitope on the TSH receptor is not associated with the ophthalmopathy of Graves' disease. However, the possibility cannot be excluded that other functional (or even nonfunctional receptor autoantibodies that are not detectable by present assays) may still play a role in the pathogenesis of Graves' ophthalmopathy.