IDENTIFICATION OF THE THYROID NA+ I- COTRANSPORTER AS A POTENTIAL AUTOANTIGEN IN THYROID AUTOIMMUNE-DISEASE/

The thyroid gland is the target of several autoimmune diseases. Specif ic thyroid proteins have been identified as autoantigens associated wi th these diseases (e.g. thyroperoxidase, thyroglobulin and the thyrotr ophin (TSH) receptor). In this paper, we report that the serum of a pa tient suffering from Hashimoto's thyroiditis, autoimmune gastritis and rheumatoid arthritis was able to inhibit the chronic TSH-induced I- u ptake of dog thyrocytes in culture, even at a 1 : 1000-fold dilution, without affecting their Rb-86(+) uptake, This blocking activity is rar e as 147 sera (from patients positive for antibodies to the thyroid mi crosomes and the gastric parietal cell antigen, patients with Sjogren' s syndrome, patients with a high titre of microsomal antibodies and lo w or negative for antibodies to thyroperoxidase, and patients with a h igh titre of microsomal antibodies and frank hypothyroidism) were nega tive when tested for their ability to inhibit I- uptake. Subsequently we tested 20 murine monoclonal antibodies previously obtained by immun izing mice with a crude human thyroid membrane preparation, which were all negative when tested against thyroglobulin and thyroperoxidase. O ne of the monoclonal antibodies displayed a 50% inhibition of the chro nic TSH-induced I-125(-) uptake of dog thyrocytes without affecting th e Rb-86(+) uptake of the cells. Immunoglobulins purified from the asci te fluid by affinity chromatography on a protein A cellulose column ha d the same characteristics. Taken together, the data suggest that thyr oidal I-125(-) uptake can be inhibited by antibodies, that autoantibod ies in the patient's serum are most probably responsible for the obser ved inhibition and therefore that the Na+/I- cotransporter is probably an autoantigen.