title: Low frequency of autoantibodies to the human Na(+)/I(-) symporter in patients with autoimmune thyroid disease.
abstract: 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 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 [(35)S]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.
authors.affiliation: German Diabetes Research Institute and Department of Endocrinology, University of Dusseldorf, Dusseldorf, Germany. sei@dfi.uniduesseldorf.de
authors.forename: J
authors.initials: J
authors.lastname: Seissler
authors.forename: S
authors.initials: S
authors.lastname: Wagner
authors.forename: M
authors.initials: M
authors.lastname: Schott
authors.forename: M
authors.initials: M
authors.lastname: Lettmann
authors.forename: J
authors.initials: J
authors.lastname: Feldkamp
authors.forename: W A
authors.initials: WA
authors.lastname: Scherbaum
authors.forename: N G
authors.initials: NG
authors.lastname: Morgenthaler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis*; D002352:Carrier Proteins / Q000276:immunology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006111:Graves Disease / Q000276:immunology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D011869:Radioligand Assay; D011994:Recombinant Proteins / Q000276:immunology; D027981:Symporters; D013967:Thyroiditis, Autoimmune / Q000276:immunology*; D000099209:Sodium-Iodide Symporters
chemical_list: D001323:Autoantibodies; D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D011994:Recombinant Proteins; D027981:Symporters; D000099209:Sodium-Iodide Symporters