Increases of the Th1/Th2 Cell Ratio in Severe Hashimoto's Disease and in the Proportion of Th17 Cells in Intractable Graves' Disease

Background: T helper type 1 (Th1), Th2, and Th17 cells produce interferon (IFN)-gamma, interleukin (IL)-4, and IL-17A, respectively. We reported that IFN-gamma and IL-4 gene polymorphisms, which are related to higher IFN-g and lower IL-4 production, respectively, are more frequent in patients with severe Hashimoto's disease (HD) than in those mild HD. We now aim to investigate the proportion of peripheral Th1, Th2, and Th17 cells in patients with autoimmune thyroid disease (AITD). Methods: We studied 17 patients with HD who developed hypothyroidism and were treated with l-thyroxine, referred to as severe HD; 17 untreated patients with HD who were euthyroid, referred to as mild HD; 18 euthyroid patients with Graves' disease (GD) who remained positive for anti-thyrotropin receptor antibody (TRAb) despite being treated with anti-thyroid drugs for more than 5 years, referred to as intractable GD; and 17 patients with GD who were euthyroid and negative for TRAb for more than 2 years after cessation of antithyroid drugs, referred to as GD in remission; and 10 control subjects without AITD. By the definitions in this study Th1 cells were CD4(+)IFN-gamma+IL-4(-)IL-17A(-) cells, Th2 cells were CD4(+)IFN-gamma-IL-4(+)IL-17A(-) cells, and CD4(+)IFN-gamma-IL-4(+)IL-17A(+) cells were Th17 cells. Results: The proportion of peripheral Th1 cells was higher in patients with severe HD than in patients with mild HD (p < 0.05), and the proportion of peripheral Th2 cells was lower in patients with severe HD than in patients with mild HD (p < 0.001). Therefore the Th1/Th2 ratio was higher in severe than in mild HD patients (p < 0.001). The proportion of peripheral Th17 cells in patients with AITD was higher than in control subjects and the proportion of these cells in patients with intractable GD was higher than in patients with GD in remission (p < 0.05). Conclusions: The peripheral Th1/Th2 cell ratio is related to the severity of HD, and the proportion of Th17 cells is related to the intractability of GD. We hypothesize that these patterns of peripheral Th cell subsets may be expressed within the thyroid.