Biological activity of autoantibodies associated with Graves' dermopathy

To test the hypothesis that Graves' dermopathy is due to cross-reactivity of thyroid autoantibody(ies) with a cellular target in pretibial skin, we tested the serum and serum immunoglobulin fraction of 20 such patients for their effects on the metabolic activities of cultured thyrocytes (rat FRTL cells), human pretibial skin fibroblasts, and human fibroblasts of other origins. The incorporation of 3H-labeled thymidine, amino acids, and glucosamine into DNA, protein, and glycosaminoglycans, respectively, was measured. TSH and the serum of each of the 20 patients with Graves' dermopathy markedly stimulated the synthesis of DNA, protein, and glycosaminoglycans by FRTL cells, but not by fibroblasts, whereas assays of serum from 38 of 40 patients with Graves' disease without dermopathy did not stimulate these processes in FRTL cells more than normal serum. Stimulatory activity was associated with immunoglobulins. Serum dermopathy-associated antibodies disappeared with the disappearance of the skin lesions. These results suggest that the serum of patients with dermopathy contains antibodies that recognize a component of the TSH receptor different from that recognized by serum of Graves' patients without dermopathy, the former acting in some manner to induce lesions in pretibial skin. The skin target remains unidentified.