Low frequency of autoantibodies to the human Na+/I- symporter in patients with autoimmune thyroid disease

Several studies suggest that the sodium-iodide symporter (NIS) may represen t a major autoantigen in autoimmune diseases of the thyroid. The aim of the present paper was to investigate the importance of autoantibodies to human NIS (hNIS-Ab) in patients suffering from Hashimoto's thyroiditis (HT) and Graves' disease (GD). Full-length human NIS (hNIS) was cloned from thyroid tissue, expressed by in vitro transcription and translation in the presence of [S-35]methionine, and used to analyze autoantibodies in a direct bindin g assay. The structurally similar glucose transporter, GLUT-2, was produced in the same system as control protein. Autoradiography revealed that full- length hNIS was expressed, recognized by a NIS monoclonal antibody, and str ongly bound by some sera from patients with autoimmune thyroid disease, whi ch did not react with the GLUT-2 control protein. Using the 95.2th percenti le of healthy controls as threshold for positivity, 19 of 177 (10.7%) patie nts with GD and 15 of 72 (20.8%) patients with HT had hNIS-Ab, respectively . Applying more stringent cut-off criteria (99.4th percentile of normal con trols), hNIS-Ab were found in only 5.6% of patients with GD and 6.9% of pat ients with HT. In HT significantly higher hNIS-Ab levels were observed comp ared with GD and normal controls (P < 0.001). There was no correlation betw een hNIS-Ab and TSH receptor antibodies and only a weak correlation to thyr oid peroxidase antibodies (P < 0.05). Comparison of hNIS-Ab, thyroid peroxi dase, and TSH receptor antibodies in individual sera revealed that the addi tional detection of hNIS-Ab did not increase the diagnostic power for GD or HT. Our data indicate that hNIS is not a major antigen in autoimmune thyro id disease, as it is the target of humoral autoimmunity in only a few patie nts with GD and HT. The frequency of hNIS-Ab may be lower than that reporte d in previous studies.