THYROTROPIN RECEPTOR AUTOANTIBODIES RECOGNIZING 2 DIFFERENT EPITOPES ON THE TSH RECEPTOR - LACK OF RELATIONSHIP TO PATIENT AGE, SEX, AND OPHTHALMOPATHY

The existence of two populations of stimulatory TSH receptor autoantib odies against different epitopes raises the possibility of a link betw een one type of autoantibody and the clinical manifestations of Graves ' disease. To test this hypothesis, serum immunoglobulins from 48 pati ents with Graves' disease were assayed for TSH binding inhibition (TBI ) activity with two different recombinant TSH receptor variants (TSH-L HR-6 and TSH-LHR-6-A1) expressed on Chinese hamster ovary cells. The a ctivity of 27 of the 48 patients' immunoglobulin samples was significa ntly less (difference in TBI value of 9% or greater) with chimera 6-A1 than with chimera 6. No immunoglobulin sample had significantly great er TSH binding inhibitory activity with chimera 6-A1 than with chimera 6. Sensitivity to the 6-A1 epitope substitution did not correlate wit h patient age, sex, or the presence or absence of hyperthyroidism. Fur ther, there was no segregation of individual patients with TSH recepto r autoantibodies with 6-A1 epitope sensitivity in terms of the past or present occurrence of ophthalmopathy, including the severity (total e ye score), clinical activity, duration, and type of therapy. These dat a indicate that recognition by autoantibodies of the 6-A1 epitope on t he TSH receptor is not associated with the ophthalmopathy of Graves' d isease. However, the possibility cannot be excluded that other functio nal (or even nonfunctional receptor autoantibodies that are not detect able by present assays) may still play a role in the pathogenesis of G raves' ophthalmopathy.