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The Modulation of the Human Sodium Iodide Symporter Activity by Graves’ Disease Sera¹

Department of Medicine (R.A.A., C.F., R.A.M., P.F.W., A.P.W.), University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Sheffield S5 7AU, United Kingdom; and Department of Pathology (M.C., M.L.), University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom

Address all correspondence and requests for reprints to: A. P. Weetman, Department of Medicine, University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Sheffield S5 7AU, United Kingdom.

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 µmol/L, respectively, and reaching complete inhibition at 20 µmol/L and 500 µmol/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 µmol/L and reaching maximum inhibition at 1600 µmol/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.

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