Chin H S, Chin D K, Morgenthaler N G, Vassart G, Costagliola S
IRIBHN, Faculty of Medicine, Free University of Brussels, Belgium.
J Clin Endocrinol Metab. 2000 Oct;85(10):3937-40. doi: 10.1210/jcem.85.10.6884.
The search for antibody against the Na+/I- symporter (NIS) has seen conflicting results over the years. Prior to cloning of NIS, Raspe et al found iodide uptake inhibiting sera were rare in autoimmune thyroid diseases (AITD) while post-cloning, others reported the presence of antibody in 12-15% of Hashimoto's thyroiditis (HT) and 30-84% of Graves' disease (GD). To evaluate the role of NIS as a potential antigen in AITD, a stable COS 7 cell line expressing high level of functional hNIS was established which allowed the screening of large number of sera for iodide uptake inhibiting activity in a 96-well plate format. Five hundred and fourteen serum samples taken from normal subjects and patients with AITD, non-autoimmune thyroid diseases, and non-thyroid autoimmune diseases were assayed for presence of iodide uptake inhibiting activity. Under the influence of these sera, iodide uptake showed a normal frequency distribution and diminution of uptake 2 SDs below the mean of controls was observed with 14 sera. Among these, 7 that were available for further study were re-evaluated after dialysis and/or Ig G extraction. All 7 sera lost their iodide uptake inhibiting activity, indicating that the effects were not antibody mediated and unknown serum factors had been responsible. In conclusion, contrary to previous results, the present study indicates that antibodies capable of modulating NIS activity are rare in AITD.
多年来，针对钠/碘同向转运体（NIS）抗体的研究结果一直存在矛盾。在NIS克隆之前，拉斯佩等人发现自身免疫性甲状腺疾病（AITD）中抑制碘摄取的血清很少见，而在克隆之后，其他人报告在12%至15%的桥本甲状腺炎（HT）和30%至84%的格雷夫斯病（GD）中存在抗体。为了评估NIS作为AITD潜在抗原的作用，建立了一个稳定表达高水平功能性人NIS的COS 7细胞系，这使得能够以96孔板形式筛选大量血清的碘摄取抑制活性。对从正常受试者以及患有AITD、非自身免疫性甲状腺疾病和非甲状腺自身免疫性疾病的患者采集的514份血清样本进行了碘摄取抑制活性检测。在这些血清的影响下，碘摄取呈现正常的频率分布，14份血清观察到摄取量减少至低于对照组平均值2个标准差。其中，可用于进一步研究的7份血清在透析和/或提取IgG后重新进行了评估。所有7份血清均失去了碘摄取抑制活性，这表明这些影响不是由抗体介导的，而是由未知的血清因子导致的。总之，与之前的结果相反，本研究表明在AITD中能够调节NIS活性的抗体很少见。
