Graves病患者外周血FOXP3、GITR及CD25基因的表达
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摘要
【目的】研究Graves病不同阶段患者外周血叉状头／翅膀状螺旋转录因子(forkhead box protein 3, FOXP3)、糖皮质激素诱导肿瘤坏死因子受体(glucocorticoid-induced tumor necrosis factor receptor, GITR)及IL-2受体α链(interleukin-2-receptor a-chain, CD25)基因的表达变化,探讨其在Graves病发病机制中的作用。
【方法】收集90例自2009年2月至2009年7月在山东大学齐鲁医院门诊就诊的Graves病患者,所有患者均符合Graves病的诊断标准：①临床甲亢的症状和体征；②甲状腺弥漫性肿大(触诊和B超证实),少数病例可以无甲状腺肿大；③血清TSH浓度降低,甲状腺激素浓度升高；④排除其他甲状腺疾病。入选者均除外肝肾疾病,恶性肿瘤及其他传染性疾病,未用其他免疫抑制剂,按病情分为Graves病初诊组30例(男13例,女17例)；Graves病缓解组30例(男10例,女20例)；Graves病复发组30例(男11例,女19例)。健康查体者30例(男14例,女16例)作为正常对照组,均来自我院自2009年2月至2009年7月健康查体人群。应用实时荧光定量PCR法检测各组外周血单个核细胞中FOXP3、GITR及CD25 mRNA含量,同时利用电化学发光的方法测定各组血清甲状腺激素水平及甲状腺过氧化酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)的水平。【结果】Graves病各组患者外周血FOXP3 mRNA表达较健康对照组均显著降低(P<0.05),缓解组FOXP3 mRNA水平与初诊组相比显著升高(P<0.05),复发组FOXP3mRNA水平虽低于缓解组(P<0.05),但明显高于初诊组(P<0.05)；Graves病各组女性患者FOXP3mRNA表达水平显著高于男性患者(P<0.05)；Graves病初诊及复发组GITR mRNA、CD25mRNA表达水平显著高于对照组(P<0.05)。
【结论】FOXP3、GITR及CD25基因可能参与了Graves病的发生、发展及复发过程。
[Objective] To investigate the roles of FOXP3, GITR and CD25 genes in the pathogenesis of different stages of Graves'disease.
[Methods] From February 2009 to July 2009 in Qilu Hospital affiliated to Shandong University, Ninty cases of Graves'disease were collected. All the patients were out-patients and consistent with Graves'disease diagnostic criteria:(1) clinical symptoms and signs of hyperthyroidism; (2) diffuse thyroid enlargement (palpation or ultrasoud-confirmed), a small number of cases can be no goiter; (3) lower serum TSH concentration, and thyroid hormone concentration increased. (4) exclude other thyroid diseases. Patients were selected except for liver and kidney disease, malignant tumors and other infectious diseases, not using other immunosuppressive agents. All objects were divided into three groups:30 cases of newly diagnosed of Graves'disease (13 men, 17 women); 30 cases of disease remission group (10 men,20 women); 30 cases of disease recurrence group (11 men,19 women).30 normal persons (14 men,16 women) served as healthy controls. The levels of FOXP3, GITR and CD25mRNA in peripheral blood mononuclear cells were measured by Light Cycler fluorescence quantitative PCR instrument, and the levels of serum thyroid hormone, TPOAb and TGAb were measured by electrochemiluminescence.
[Results] The level of FOXP3 mRNA in each Graves'disease group was significantly lower than that of healthy controls (P<0.05), the FOXP3 mRNA level in the remission group was significantly higher than that of the newly diagnosed group (P<0.05), and the FOXP3 mRNA level in the recurrence group was lower than that of the remission group (P<0.05) but higher than that of the newly diagnosed group (P<0.05). The level of FOXP3 mRNA in female Graves'disease patients was significantly higher than that of male Graves'disease patients (P<0.05). The levels of GITR mRNA and CD25 mRNA in the newly diagnosed and the recurrence groups increased compared with that in the healthy controls (P<0.05).
[Conclusions] The FOXP3, GITR and CD25 genes may be involved in the process of Graves'disease and its recurrence.
【方法】收集90例自2009年2月至2009年7月在山东大学齐鲁医院门诊就诊的Graves病患者,所有患者均符合Graves病的诊断标准：①临床甲亢的症状和体征；②甲状腺弥漫性肿大(触诊和B超证实),少数病例可以无甲状腺肿大；③血清TSH浓度降低,甲状腺激素浓度升高；④排除其他甲状腺疾病。入选者均除外肝肾疾病,恶性肿瘤及其他传染性疾病,未用其他免疫抑制剂,按病情分为Graves病初诊组30例(男13例,女17例)；Graves病缓解组30例(男10例,女20例)；Graves病复发组30例(男11例,女19例)。健康查体者30例(男14例,女16例)作为正常对照组,均来自我院自2009年2月至2009年7月健康查体人群。应用实时荧光定量PCR法检测各组外周血单个核细胞中FOXP3、GITR及CD25 mRNA含量,同时利用电化学发光的方法测定各组血清甲状腺激素水平及甲状腺过氧化酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)的水平。【结果】Graves病各组患者外周血FOXP3 mRNA表达较健康对照组均显著降低(P<0.05),缓解组FOXP3 mRNA水平与初诊组相比显著升高(P<0.05),复发组FOXP3mRNA水平虽低于缓解组(P<0.05),但明显高于初诊组(P<0.05)；Graves病各组女性患者FOXP3mRNA表达水平显著高于男性患者(P<0.05)；Graves病初诊及复发组GITR mRNA、CD25mRNA表达水平显著高于对照组(P<0.05)。
【结论】FOXP3、GITR及CD25基因可能参与了Graves病的发生、发展及复发过程。
[Objective] To investigate the roles of FOXP3, GITR and CD25 genes in the pathogenesis of different stages of Graves'disease.
[Methods] From February 2009 to July 2009 in Qilu Hospital affiliated to Shandong University, Ninty cases of Graves'disease were collected. All the patients were out-patients and consistent with Graves'disease diagnostic criteria:(1) clinical symptoms and signs of hyperthyroidism; (2) diffuse thyroid enlargement (palpation or ultrasoud-confirmed), a small number of cases can be no goiter; (3) lower serum TSH concentration, and thyroid hormone concentration increased. (4) exclude other thyroid diseases. Patients were selected except for liver and kidney disease, malignant tumors and other infectious diseases, not using other immunosuppressive agents. All objects were divided into three groups:30 cases of newly diagnosed of Graves'disease (13 men, 17 women); 30 cases of disease remission group (10 men,20 women); 30 cases of disease recurrence group (11 men,19 women).30 normal persons (14 men,16 women) served as healthy controls. The levels of FOXP3, GITR and CD25mRNA in peripheral blood mononuclear cells were measured by Light Cycler fluorescence quantitative PCR instrument, and the levels of serum thyroid hormone, TPOAb and TGAb were measured by electrochemiluminescence.
[Results] The level of FOXP3 mRNA in each Graves'disease group was significantly lower than that of healthy controls (P<0.05), the FOXP3 mRNA level in the remission group was significantly higher than that of the newly diagnosed group (P<0.05), and the FOXP3 mRNA level in the recurrence group was lower than that of the remission group (P<0.05) but higher than that of the newly diagnosed group (P<0.05). The level of FOXP3 mRNA in female Graves'disease patients was significantly higher than that of male Graves'disease patients (P<0.05). The levels of GITR mRNA and CD25 mRNA in the newly diagnosed and the recurrence groups increased compared with that in the healthy controls (P<0.05).
[Conclusions] The FOXP3, GITR and CD25 genes may be involved in the process of Graves'disease and its recurrence.
引文
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