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.

Changes of Thyroidal Tc-99m Tetrofosmin Uptake and Wash-Out in Patients with Hashimoto’s Thyroiditis

“…In the euth yro id gro up, the po si ti ve cor re la ti ons of Tc-99m tet ro fos min up ta ke with an ti-TPO an ti body le vels and thyro id vo lu mes sug ges ted the ac ti ve inf lamma tory pro cess. Our fin dings sup port the re sults of Bog ner et al 28 They re por ted that mic ro so mal an tibo di es we re res pon sib le for the cyto to xic ef fect, whe re as thyrog lo bu lin an ti bo di es did not me di a te cyto to xi city. On the ot her hand, si mi lar to the results of Ri e u et al, 29 we did not find any re la ti ons hip bet we en thyro id vo lu me and an ti-TPO an ti body in euth yro id or hypoth yro id pa ti ents.…”

Thyroid hormones and cognitive functioning in healthy, euthyroid women: A correlational study

“…Thyroid antibodies can bind to the enzymes essential for T4 and T3 synthesis and either enhance their actions leading to overproduction of T4 and T3 as in Graves's disease (Burman and Baker, 1985) or block their function, as in Hashimoto's thyroiditis, an autoimmune disease that results in hypothyroidism (Bogner et al, 1984).…”

Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a dominant conformational epitope on human thyroid peroxidase.

“…Until the demonstration of their identity (3)(4)(5)(6)(7), TPO was studied as the "thyroid microsomal antigen" (8). IgG class autoantibodies with high affinity for TPO (9) are present in the sera of patients with Hashimoto's thyroiditis or Graves' disease and may play a role in thyroid destruction (8,(10)(11)(12).…”