Liu Hai-Yan, Shi Zhi-Yong, Fan Di, Zhang Sheng-Xiao, Wu Li-Xiang, Lu Ke-Yi, Yang Su-Yun, Li Wan-Ting, Kang Jing-Fen, Li Cai-Hong, Cheng Zhe-Hao, Xue Yan, Wu Zhi-Fang, Li Xiao-Feng, Li Si-Jin
Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan, China.
Department of Rheumatology, Second Hospital of Shanxi Medical University, Taiyuan, China.
Mol Immunol. 2022 Apr;144:49-57. doi: 10.1016/j.molimm.2022.02.004. Epub 2022 Feb 18.
Graves' disease (GD) is one of the most common autoimmune conditions, but the mechanisms underlying the associated induction of autoimmunity are not known. We explored the role of peripheral lymphocyte subpopulations in disease pathogenesis.
In total, 32 patients and 40 age- and sex-matched healthy controls were recruited in this study. Peripheral levels of T, B, NK, CD4 T, CD8 T, Th1, Th2, Th17, and Treg cells were measured using flow cytometry. For all patients, we compared all lymphocyte subpopulations between GD patients and healthy controls. Changes in patient lymphocyte subsets were compared before and after treatment.
The absolute numbers of circulating Th17 cells (0.45 ± 1.16, p > 0.05) between GD patients and healthy controls were not significantly different. However, the percentage of Th17 cells was significantly increased (0.25 ± 0.11, p < 0.05). The absolute numbers and percentages of circulating Tregs in GD patients were significantly decreased compared with those in healthy participants (11.61 ± 2.75, p < 0.05). There was a significant difference in Treg absolute numbers between the untreated and drug-treated groups. Furthermore, we found that the Treg percentage in untreated patients (mean=4.78) was not significantly different from that in the drug-treated group (mean=4.81). In addition, circulating Treg absolute numbers in GD patients with exophthalmos were significantly lower than those in GD patients without exophthalmos (9.96 ± 4.16, p < 0.05). A similar trend was observed in GD patients with weight loss (11.97 ± 3.28, p < 0.05).
GD pathogenesis was associated with a lower Treg population and an increased Th17/Treg ratio (T helper cell 17/ regulatory T cells). Th17 cells in this study were not related to the disease. Furthermore, anti-thyroid drug therapy improved immune-mediated system disorders. Finally, we found lower absolute numbers of circulating Tregs in GD patients with certain positive signs, such as exophthalmos and/or weight loss. Thus, immune changes are correlated with partial clinical manifestations.
格雷夫斯病（GD）是最常见的自身免疫性疾病之一，但自身免疫相关诱导机制尚不清楚。我们探讨了外周淋巴细胞亚群在疾病发病机制中的作用。
本研究共招募了32例患者和40名年龄及性别匹配的健康对照者。采用流式细胞术检测外周血T、B、NK、CD4 T、CD8 T、Th1、Th2、Th17和调节性T细胞（Treg）水平。对于所有患者，我们比较了GD患者和健康对照者之间的所有淋巴细胞亚群。比较了患者治疗前后淋巴细胞亚群的变化。
GD患者与健康对照者之间循环Th17细胞的绝对数量（0.45±1.16，p>0.05）无显著差异。然而，Th17细胞的百分比显著增加（0.25±0.11，p<0.05）。与健康参与者相比，GD患者循环Treg的绝对数量和百分比显著降低（11.61±2.75，p<0.05）。未治疗组和药物治疗组之间Treg绝对数量存在显著差异。此外，我们发现未治疗患者的Treg百分比（平均值=4.78）与药物治疗组（平均值=4.81）无显著差异。此外，有突眼的GD患者循环Treg绝对数量显著低于无突眼的GD患者（9.96±4.16，p<0.05）。体重减轻的GD患者也观察到类似趋势（11.97±3.28，p<0.05）。
GD发病机制与较低的Treg数量和升高的Th17/Treg比值（辅助性T细胞17/调节性T细胞）有关。本研究中的Th17细胞与疾病无关。此外，抗甲状腺药物治疗改善了免疫介导的系统紊乱。最后，我们发现有某些阳性体征（如突眼和/或体重减轻）的GD患者循环Treg绝对数量较低。因此，免疫变化与部分临床表现相关。
