PREVALENCE AND SIGNIFICANCE OF ANTIBODIES REACTIVE WITH EYE MUSCLE MEMBRANE-ANTIGENS IN SERA FROM PATIENTS WITH GRAVES OPHTHALMOPATHY AND OTHER THYROID AND NONTHYROID DISEASES

We have investigated the antibody responses made to porcine eye muscle antigens by sera from patients with Graves' disease and ophthalmopath y (GO) on Western blotting in a retrospective cross sectional study. R eactivity to several different eye muscle antigens was observed; howev er, antibodies to two antigens of 64 and 95 kd were found predominantl y in sera with a prevalence of 63.6% (14/22) and 50.0% (11/22), respec tively. In Graves' patients without GO the levels dropped to 18.2% (6/ 33) and 9.1% (3/33), and to 10.0% (2/20) and 20.0% (4/20) in patients with other thyroid diseases, and 0% (0/29) and 20.7% (6/29) in patient s with nonthyroid diseases. Healthy control subjects gave positive res ponses in 8.0% (2/25) and 12.0% (3/25) of sera tested against the two antigens. The prevalence of the responses in patients with GO was sign ificantly different when compared with normals and other patient group s (p < 0.05 and p < 0.01). All patients with ophthalmopathy graded cla ss 3 or 4 and most of the patients with GO and a suppressed thyrotropi n (TSH) value at the time of investigation reacted with one or other o f the two antigens. Similar prevalences of response were found to the 64 and 95 antigens in those patients with GO whether they were thyrotr opin receptor antibodies (TSHR-Ab) positive or negative (p > 0.05). Ho wever, the prevalence of the response to the 64 kd antigen in the TSHR -Ab positive group of patients without GO (31.3%) was significantly hi gher than that found in the TSHR-Ab negative (5.9%, p < 0.05) group. 8 1.8% (9/11) of patients with GO and a suppressed TSH recognized the 64 kd antigen compared with 45.5% with a normal TSH value (p < 0.05) and 16.7% without GO and a normal TSH (p < 0.01). In additional studies w e have shown that a mouse monoclonal antibody (3B12) raised to the ext racellular domain of the human TSH receptor also reacted with a 55 kd antigen in pig eye muscle but was not inhibited from its binding to ei ther pig eye antigen or human TSH receptor antigen (3A1) by any of our patients' sera. These data suggest that serum antibodies reactive wit h porcine eye muscle antigens are potentially useful markers of ophtha lmopathy in Graves' patients and should be further evaluated in longit udinal studies to see if they can predict the onset or regression of G raves' ophthalmopathy.