Autoimmunity involving the human sodium/iodide symporter: fact or fiction?

Presence, functional activity and clinical relevance of autoantibodies directed against the human sodium iodide symporter (NIS) in thyroid autoimmune diseases have become the subject of much controversy in recent years. Earlier reports have claimed that NIS may represent a major thyroid autoantigen that elicits formation of functionally relevant autoantibodies in a significant proportion of patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT). Moreover, a recent study has extended this notion by reporting detection of NIS-autoantibodies in 22% and 24% of a small number of patients with GD and HT, respectively, but not in patients with other autoimmune diseases. However, in striking contrast to these reports, two independent groups of investigators have now presented convincing evidence that NIS-directed autoantibodies occur with low frequency among a large sample of patients with autoimmune thyroid diseases. Moreover, no evidence of specific iodide uptake inhibiting activity was obtained once sera had been subjected to dialysis and/or IgG extraction. Thus, although the controversy has not been definitively resolved, hNIS does not appear to be a major functionally relevant antigen in autoimmune thyroid diseases. Moreover, when detected in addition to TPO and TSH receptor autoantibodies, NIS-directed autoantibodies do not appear to contribute any diagnostic power for GD and HT.