ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY AGAINST ORBITAL TARGET-CELLS IN THYROID-ASSOCIATED OPHTHALMOPATHY AND RELATED DISORDERS - CLOSE RELATIONSHIP BETWEEN SERUM CYTOTOXIC ANTIBODIES AND PARAMETERS OF EYE MUSCLE DYSFUNCTION

We have carried out tests for antibody-dependent cell-mediated cytotox icity (ADCC) against extra ocular muscle (EOM), Muller's muscle, orbit al fibroblasts and skeletal muscle in patients with thyroid-associated ophthalmopathy (TAO) and related eye disorders, Cytotoxicity was meas ured as lactate dehydrogenase (LDH) release and results expressed as % cytotoxicity. Tests were positive, with EOM cells, in 65% of patients with TAO, 75% with ocular myopathy, a variant of TAO in which periorb ital inflammation is minimal, 50% with euthyroid Graves' disease defin ed as ophthalmopathy associated with subclinical thyroiditis and in 50 % of patients with stable lid lag and retraction but no other signs of progressive ophthalmopathy, but in only 13% of patients with Graves' hyperthyroidism without ophthalmopathy, 10% with Hashimoto's thyroidit is and 14% of patients with other thyroid disorders, Tests were positi ve, with Muller's muscle cells, in 40% of patients with TAO, 25% with ocular myopathy, 40% with euthyroid Graves' disease, 44% with lid lag, 19% with Graves' hyperthyroidism, 50% with Hashimoto's thyroiditis an d in 37.5% of patients with other thyroid disorders. When skeletal mus cle cells were used as target, tests were positive in 13% of patients with TAO, 31% with lid lag, 25% with Graves' hyperthyroidism and in 29 % of patients with Hashimoto's thyroiditis, but in no patient with eut hyroid Graves' disease or other thyroid disorders, Tests were negative in all patients and normals tested when EOM-derived fibroblasts were used as targets in ADCC, A significant positive correlation between % cytotoxicity against EOM cells and the severity of the eye muscle dysf unction expressed as an eye muscle index, was observed in patients wit h TAO. There was a significant negative correlation between the durati on of eye disease and % cytotoxicity against EOM cells, suggesting hig her titers of cytotoxic antibodies in the early stages of TAO, There w as no correlation between % cytotoxicity and serum level of anti-TSH r eceptor antibodies, measured in a radioreceptor assay, These findings suggest that autoimmunity against Muller's muscle may play a role in t he pathogenesis of persistent lid lag and retraction, The nature of th e EOM and Muller's muscle autoantigens recognized by cytotoxic antibod ies in the serum of patients with TAO and related eye disorders is unk nown.