Antibody-dependent cell mediated cytotoxicity against human thyroid cells in Hashimoto's thyroiditis but not Graves' disease

Abstract

Antibody-dependent cell-mediated cytotoxicity (ADCC) against human thyroid cell targets was measured in a chromium release assay, using serum from patients with autoimmune thyroid diseases. The source of effector cells was peripheral blood mononuclear cells from normal subjects. Mean (+/- SD) specific lysis produced by serum from patients with Hashimoto's thyroiditis was 27.3 +/- 6.1%, compared to 10.6 +/- 4.7% produced by serum from normal subjects and 13.3 +/- 10% using serum from patients with Graves' hyperthyroidism. Cytotoxicity using serum from hyperthyroid patients was not different after treatment. Thyroid cell targets from histologically different thyroid cell preparations (Graves' disease, multinodular goiter, normal thyroid) were equally sensitive to killing, although cells from a benign thyroid adenoma were much less sensitive. A strong positive correlation was found between percent specific lysis and titers of serum microsomal antibody. By addition of patients' immunoglobulin to normal serum, we found that microsomal antibodies were responsible for the cytotoxic effect, whereas thyroglobulin antibodies did not mediate cytotoxicity. These results demonstrate that ADCC plays an important role in the thyroid cell destruction of chronic (Hashimoto's) thyroiditis. Although cytotoxic activity was associated with the antimicrosomal-, but not antithyroglobulin-, positive immunoglobulin G fraction, it is not clear whether the microsomal antibody itself, or an unidentified antibody occurring in the same antibody fraction, is the mediator of cytotoxicity in this disorder.