title: The modulation of the human sodium iodide symporter activity by Graves' disease sera.
abstract: The transport of iodide into the thyroid, catalyzed by the Na+/I- symporter (NIS), is the initial and rate-limiting step in the formation of thyroid hormones. To study the basic characteristics of the human (h) NIS, we have established a Chinese hamster ovary cell line stably expressing the hNIS (CHO-NIS9). In agreement with previous work on the rat NIS, iodide uptake in these cells was initiated within 2 min of the addition of 131I, reaching a plateau after 30 min. Both perchlorate and thiocyanate inhibited iodide uptake in a dose-dependent manner, with inhibition evident at concentrations of 0.01 and 0.1 micromol/L, respectively, and reaching complete inhibition at 20 micromol/L and 500 micromol/L, respectively. Ouabain, which blocks the activity of the Na+/K+ adenosine triphosphatase, also inhibited iodide uptake in a dose-dependent manner, starting at concentrations of 100 micromol/L and reaching maximum inhibition at 1600 micromol/L, indicating that iodide uptake in these cells is sodium dependent. CHO-NIS9 cells were further used to study 88 sera from patients with Graves' disease, for iodide uptake inhibitory activity, which were compared with sera from 31 controls. Significant iodide uptake inhibition was taken as any inhibition in excess of the mean + 3 SD of the results with the control sera. On this basis, 27 (30.7%) of the Graves' sera, but none of the controls, inhibited iodide uptake in CHO-NIS9. IgGs from these patients also inhibited iodide uptake, indicating that this inhibitory activity was antibody mediated. In summary, we have established a CHO cell line stably expressing the hNIS and shown that antibodies in GD sera can inhibit iodide uptake in these cells. This further emphasizes the role of NIS as a novel autoantigen in thyroid immunity.
authors.affiliation: Department of Medicine, University of Sheffield, Clinical Sciences Centre, Northern General Hospital, United Kingdom.
authors.forename: R A
authors.initials: RA
authors.lastname: Ajjan
authors.forename: C
authors.initials: C
authors.lastname: Findlay
authors.forename: R A
authors.initials: RA
authors.lastname: Metcalfe
authors.forename: P F
authors.initials: PF
authors.lastname: Watson
authors.forename: M
authors.initials: M
authors.lastname: Crisp
authors.forename: M
authors.initials: M
authors.lastname: Ludgate
authors.forename: A P
authors.initials: AP
authors.lastname: Weetman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood*; D016466:CHO Cells; D002352:Carrier Proteins / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D006224:Cricetinae; D006111:Graves Disease / Q000097:blood*; D006801:Humans; D007454:Iodides / Q000097:blood; D008565:Membrane Proteins / Q000097:blood* / Q000276:immunology; D010042:Ouabain / Q000494:pharmacology; D010472:Perchlorates / Q000494:pharmacology; D011994:Recombinant Proteins / Q000097:blood / Q000276:immunology; D017670:Sodium Compounds / Q000494:pharmacology; D027981:Symporters; D013861:Thiocyanates / Q000494:pharmacology; D014162:Transfection; D000099209:Sodium-Iodide Symporters
chemical_list: D000906:Antibodies; D002352:Carrier Proteins; D007454:Iodides; D008565:Membrane Proteins; D010042:Ouabain; D010472:Perchlorates; D011994:Recombinant Proteins; D017670:Sodium Compounds; D027981:Symporters; D013861:Thiocyanates; D000099209:Sodium-Iodide Symporters; C031068:sodium perchlorate; C031760:thiocyanate