Increases of the Th1/Th2 Cell Ratio in Severe Hashimoto's Disease and in the Proportion of Th17 Cells in Intractable Graves' Disease
Increases of the Th1/Th2 Cell Ratio in Severe Hashimoto's Disease and in the Proportion of Th17 Cells in Intractable Graves' Disease
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DOI：
10.1089/thy.2008.0423
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发表时间：
2009-05-01
期刊：
影响因子：
6.6
通讯作者：
Iwatani, Yoshinori
中科院分区：
文献类型：
--
作者：
Nanba, Takashi;Watanabe, Mikio;Iwatani, Yoshinori
背景：辅助性T细胞1型（Th 1）、Th 2和Th 17细胞分别产生干扰素（IFN）-γ、白细胞介素（IL）-4和IL-17 A。我们报道了IFN-γ和IL-4基因多态性，这是与较高的IFN-γ和较低的IL-4的生产，分别是更常见的严重桥本病（HD）患者比那些轻度HD。我们现在的目的是研究自身免疫性甲状腺疾病（AITD）患者外周血Th 1、Th 2和Th 17细胞的比例。方法：我们研究了17例发生甲状腺功能减退并接受左旋甲状腺素治疗的HD患者（称为重度HD）、17例甲状腺功能正常但未经治疗的HD患者（称为轻度HD）、17例甲状腺功能正常但未经治疗的HD患者（称为轻度HD）、17例甲状腺功能正常但未经治疗的HD患者（称为轻度HD）和17例甲状腺功能正常但未经治疗的HD患者（称为轻度HD）。18例甲状腺功能正常的Graves病（GD）患者，尽管使用抗甲状腺药物治疗超过5年，但抗促甲状腺素受体抗体（TRAb）仍为阳性，称为难治性GD; 17例GD患者在停用抗甲状腺药物后甲状腺功能正常且TRAb阴性超过2年，称为GD缓解期; 10例对照受试者无AITD。根据本研究中的定义，Th 1细胞为CD 4（+）IFN-γ +IL-4（-）IL-17 A（-）细胞，Th 2细胞为CD 4（+）IFN-γ-IL-4（+）IL-17 A（-）细胞，并且CD 4（+）IFN-γ-IL-4（+）IL-17 A（+）细胞为Th 17细胞。重型HD患者外周血Th 1细胞比例高于轻型HD患者重型HD患者外周血Th 2细胞比例低于轻型HD患者（p < 0.001）。因此，重型HD患者Th 1/Th 2比值高于轻型HD患者（p < 0.001）。AITD患者外周血Th 17细胞比例高于对照组，难治性GD患者外周血Th 17细胞比例高于缓解期GD患者（p < 0.05）。结论：外周血Th 1/Th 2细胞比例与HD的严重程度有关，Th 17细胞比例与GD的难治性有关。我们推测这些外周Th细胞亚群的模式可能在甲状腺内表达。
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.