Antithyrotropin Antibodies in the Sera of Graves’Disease Patients*

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Abstract
To determine the presence and potential importance of antiidiotypic antibodies (anti-id) in the immune regulation of Graves’ disease, sera from 57 patients with Graves’ disease were screened before or during antithyroid therapy by enzyme-linked immunoabsorbent assay (ELISA) for presumptive anti-id, as defined by the presence of immunoglobulins (Igs) directed against TSH. The mean optical density, indicating the presence of TSH-binding antibodies, was 0.34 ± 0.28 (±SD) in the sera of Graves’ disease patients and 0.19 ± 0.12 in the sera of 24 normal subjects (P < 0.004). Control antigens (hCG and albumin) did not bind significant amounts of serum Igs. In 8 Graves’ patients whose sera bound TSH, 40-80% inhibition was obtained with the addition of TSH receptor-purified IgG (′1 Mg/ml) derived from a single Graves’ patient’s serum; no inhibition was found with normal IgG (′10 μg/ml). Presumptive anti-id was isolated from sera of 6 Graves’ patients by affinity purification with a TSH affinity column; the resultant IgG blocked immunoglobulin binding to the TSH receptor when added to the serum of the same patient from whom it had been isolated. The presence of anti-id correlated inversely with the presence of TSH receptor antibodies (r = -0.76; P < 0.01). These studies demonstrate that 1) significant TSH binding is present in sera from Graves’ disease patients, and 2) this TSH binding is specifically inhibitable by Graves’ IgG, but not by normal IgG. These data support the hypothesis that TSHbinding immunoglobulins may represent anti-id that are present in Graves’ disease as part of the immunological response to TSH receptor or TSH receptor antibodies. Such anti-id could modulate the expression of disease activity in Graves’ disease by altering TSH receptor antibody action or production.