Cross-reaction of eye muscle antibodies with thyroid tissue in thyroid-associated ophthalmopathy

The nature of the association of ophthalmopathy with autoimmune thyroid disease is not understood. Serum autoantibodies to eye muscle have previously been identified and in this study we have explored the hypothesis that there may be shared antigenic determinants between orbital and thyroid tissues. Sera were obtained from patients in whom eye muscle antibodies (EMAb) had been detected by an enzyme-linked immunosorbent assay (ELISA); the sera were preincubated with membrane preparations of thyroid or eye muscle, hepatic membranes being used as control. Tissue-binding antibodies were removed from serum by centrifugation and the supernatant serum was analysed using an indirect ELISA and by immunoblotting. In the ELISA, all sera gave a positive response for EMAb. In one serum, the binding was entirely non-specific. All sera showed significant neutralization of EMAb by eye muscle. In six sera there was reduction of EMAb after exposure to thyroidal antigens, indicative of cross-reaction. Western blotting confirmed the non-specific nature of the binding in one serum. In five of the remaining nine sera, protein bands were identified which interacted specifically with eye muscle and, in two of these, the same determinants were neutralized by preincubation with thyroid tissue. The Western blots confirmed the findings in the ELISA. The determinants recognized by IgG were variable between patients and no common antigen could be identified. This study demonstrates that, in some cases of thyroid-associated ophthalmopathy, there is cross-reaction of EMAb with thyroidal antigens, but this is variable and not found in every case. This may explain the association of the disease with autoimmune thyroid disease, at least in some cases.