We have studied the clinical significance of cytotoxic
antibodies against human eye muscle cells in patients with
thyroid-associated ophthalmopathy (
TAO). Eye muscle reactive
antibodies were measured in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. A positive test was defined as % specific lysis greater than the upper limit of normal, taken as the mean plus two standard deviations for normal subjects tested concurrently. As parameters of the severity of the ophthalmopathy we measured the degree of
proptosis (mm), level of intraocular pressure (IOP) (mmHg) and American Thyroid Association classes (0-6). ADCC tests were positive in 21 out of 42 patients with
TAO and in 8 out of 14 patients with
Graves' disease without evident
eye disease but in none of 12 normal subjects tested. In patients with
TAO mean (+/- SE) IOP was significantly greater than that in patients with
Graves' disease without apparent eye involvement for the primary position and for all gaze positions. There were significant positive correlations between levels of eye muscle reactive cytotoxic
antibodies and the severity of the
eye disease quantitated as American Thyroid Association classes 0-6, the IOP in the primary position and on downgaze, but not with the degree of
proptosis. These results suggest that cytotoxic
antibodies, as detected in ADCC, may play a role in the eye muscle damage of
TAO and that their measurement may provide a useful clinical test.