Thyroid binding antibodies and other immunological abnormalities in patients with Graves' ophthalmopathy: effect of treatment with cyclophosphamide.

Patients with Graves' ophthalmopathy were studied for a possible role of thyroid binding antibodies (TBAb) as measured by a radioreceptor assay, and for in vitro evidence of immunoreactivity to orbital antigens. The effect of cyclophosphamide (CY) treatment on the immunological parameters and the clinical course of the eye disease was also studied. The mean TBAb index for all patients with eye disease was significantly less than that for the normal and for patients with Graves hyperthyroidism who lacked eye disease. The mean TBAb index for patients with ophthalmopathy and past or present hyperthyroidism was significantly less than for those patients with eye disease but no associated hyperthyroidism ('euthyroid Graves' disease'). TBAb levels did not correlate with the severity of duration of the eye disease and did not change during treatment with CY. Significant titres of serum antibodies against human eye muscle extract or subcellular fractions, or macrophage inhibitory factor (MIF) production in response to human orbital tissue extract were not detected in patients with eye disease. The congestive changes improved in all patients treated with CY, although the degree of proptosis and eye muscle involvement improved in only 3 of 24 and 11 of 20 patients respectively with these abnormalities. TBAb are unlikely to play a role in the pathogenesis of Graves' ophthalmopathy and the hyperthyroidism and eye disease should be considered separate autoimmune disorders. The apparently anomalous finding of a higher mean TBAb index in patients with eye disease and hyperthyroidism than in those with hyperthyroidiam alone may reflect a more severe defect of suppressor T cell function in the former group. Because evidence for specific immunoreactivity against orbital antigens was not found in this study other approaches to defining the underlying immunological mechanisms will have to be sought.