Identification of tht thyroid Na+/I- cotransporter as a potential autoantigen in thyroid autoimmune diseases

Abstract

The thyroid gland is the target of several autoimmune diseases. Specific thyroid proteins have been identified as autoantigens associated with these diseases (e.g. thyroperoxidase, thyroglobulin and the thyrotrophin (TSH) receptor). In this paper, we report that the serum of a patient suffering from Hashimoto's thyroiditis, autoimmune gastritis and rheumatoid arthritis was able to inhibit the chronic TSH-induced I- uptake of dog thyrocytes in culture, even at a 1:1000-fold dilution, without affecting their 86Rb+ uptake. This blocking activity is rare as 147 sera (from patients positive for antibodies to the thyroid microsomes and the gastric parietal cell antigen, patients with Sjögren's syndrome, patients with a high titre of microsomal antibodies and low or negative for antibodies to thyroperoxidase, and patients with a high titre of microsomal antibodies and frank hypothyroidism) were negative when tested for their ability to inhibit I- uptake. Subsequently we tested 20 murine monoclonal antibodies previously obtained by immunizing mice with a crude human thyroid membrane preparation, which were all negative when tested against thyroglobulin and thyroperoxidase. One of the monoclonal antibodies displayed a 50% inhibition of the chronic TSH-induced 125I- uptake of dog thyrocytes without affecting the 86Rb+ uptake of the cells. Immunoglobulins purified from the ascite fluid by affinity chromatography on a protein A cellulose column had the same characteristics. Taken together, the data suggest that thyroidal 125I- uptake can be inhibited by antibodies, that autoantibodies in the patient's serum are most probably responsible for the observed inhibition and therefore that the Na+/I- cotransporter is probably an autoantigen