USE OF EYE MUSCLE ANTIBODY MEASUREMENTS TO MONITOR RESPONSE TO PLASMAPHERESIS IN PATIENTS WITH THYROID-ASSOCIATED OPHTHALMOPATHY

We have measured eye muscle antibodies, in immunoblotting, in the serum from five patients with severe ophthalmopathy associated with Graves' hyperthyroidism who underwent plasmapheresis, correlating their levels with clinical features of the eye disorder and response to treatment. Blood taken before each plasma exchange was tested in SDS-polyacrylamide gel electrophoresis and Western blotting for antibodies reactive with pig eye muscle membrane (PEMM) antigens and in a Cr-51 release assay for antibodies which are cytotoxic to human eye muscle cells in antibody-dependent cell-mediated cytotoxicity (ADCC). Antibodies reactive with a 64 kDa PEMM antigen were detected in three patients who had eye disease of less than six months duration, but not in the two with more chronic disease. Antibodies against a 95 kDa PEMM antigen were detected in one patient in whom anti-64 kDa antibodies were also demonstrated. All five patients showed significant improvement in their eye disease following plasmapheresis exchange and titres of the anti-64 kDa protein antibody decreased in the three patients with detectable levels before treatment. TSH receptor stimulating antibodies were detected in all five patients before treatment, failing during plasmapheresis in four and becoming undetectable in three by the end of treatment. There was no close correlation between levels of TSH receptor antibodies and titres of anti-64 kDa protein antibodies although both tended to fall during and following plasmapheresis. ADCC tests were negative in all five patients before plasmapheresis but, surprisingly, transiently positive in three following treatment. There was no close correlation between ADCC activity and titres of antibodies to the 64 kDa or 95 kDa proteins before plasmapheresis, or following plasma exchange, in any patient. While change in levels of antibodies reactive with a 64 kDa PEMM protein during plasma exchange paralleled clinical improvement in the small number of patients studied, this does not prove a pathogenetic role in thyroid-associated ophthalmopathy. On the other hand, measurement of antibodies reactive with a 64 kDa eye muscle membrane protein before treatment, may, along with clinical parameters, help to identify those patients with severe active ophthalmopathy likely to have a good response to plasmapheresis.