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German Diabetes Research Institute and Department of Endocrinology, University of Dusseldorf (J.S., S.W., M.S., M.L., J.F., W.A.S.), D-40225 Dusseldorf, Germany; and Research Department, B.R.A.H.M.S Diagnostica, Biotechnology Center (N.G.M.), D-16761 Hennigsdorf/Berlin, Germany
Address all correspondence and requests for reprints to: J. Seissler, M.D., German Diabetes Research Institute, University of Dusseldorf, Aufm Hennekamp 65, D-40225 Dusseldorf, Germany. E-mail: sei{at}dfi
Several studies suggest that the sodium-iodide symporter (NIS) may represent 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 Hashimotos 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 [35S]methionine, and used to analyze autoantibodies in a direct binding 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 strongly bound by some sera from patients with autoimmune thyroid disease, which did not react with the GLUT-2 control protein. Using the 95.2th percentile of healthy controls as threshold for positivity, 19 of 177 (10.7%) patients 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 controls), hNIS-Ab were found in only 5.6% of patients with GD and 6.9% of patients with HT. In HT significantly higher hNIS-Ab levels were observed compared with GD and normal controls (P < 0.001). There was no correlation between hNIS-Ab and TSH receptor antibodies and only a weak correlation to thyroid peroxidase antibodies (P < 0.05). Comparison of hNIS-Ab, thyroid peroxidase, and TSH receptor antibodies in individual sera revealed that the additional 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 thyroid disease, as it is the target of humoral autoimmunity in only a few patients with GD and HT. The frequency of hNIS-Ab may be lower than that reported in previous studies.
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