TISSUE-SPECIFICITY AND SEROLOGIC REACTIVITY OF AN AUTOANTIGEN ASSOCIATED WITH AUTOIMMUNE THYROID-DISEASE

A recent report has identified a new autoantigen called D1 that appear s to be associated with Graves' ophthalmopathy and is expressed in the thyroid and eye muscle. To better characterize the tissue specificity and disease relevance of this antigen, we evaluated the expression of Dl RNA in various human tissues using a reverse transcriptase polymer ase chain reaction assay. These studies indicate a wide tissue distrib ution of the messenger RNA for this antigen, including the thyroid, ey e muscle, parathyroid, spleen, skeletal muscle, and uterus. There were variations in the relative amounts of specific message for Dl in the different tissues, with the uterus, thyroid, and eye muscle having the greatest amount of product per microgram of total RNA. A maltose bind ing protein-Dl fusion protein was expressed in Escherichia coli, purif ied, and used to assess serologic reactivity to Dl by Western blot. Au toantibodies to this antigen were noted in 19 of 24 (78%) of Hashimoto 's disease patients, 26 of 41 (63%) of Graves' disease patients, and i n 9 of 17 (53%) of normal controls. Sixty percent of Graves' disease p atients with clinical ophthalmopathy had antibodies to D1, as did 63% of Graves' patients without signs or symptoms of clinical ophthalmopat hy. There was no correlation between reactivity to Dl and either clini cal measures of hyperthyroidism or antibody titers to thyroid peroxida se or thyroglobulin. The presence of autoantibodies to this antigen in patients with Hashimoto's disease, in Graves' disease patients withou t ophthalmopathy and in normal controls indicate that serologic recogn ition of this antigen is not restricted to patients with ophthalmopath y. In addition, the expression of messenger RNA for this antigen in mu ltiple types of cells questions the tissue specificity of this autoant igen.