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格雷夫斯病不同阶段 Th9 和 Th17 淋巴细胞及功能细胞因子的变化及其与促甲状腺激素受体抗体的关系。

Changes in Th9 and Th17 lymphocytes and functional cytokines and their relationship with thyroid-stimulating hormone receptor antibodies at different stages of graves' disease.

机构信息

Department of Endocrinology and Metabolism, Lanzhou University Second Hospital, Lanzhou, China.

出版信息

Front Immunol. 2022 Jul 22;13:919681. doi: 10.3389/fimmu.2022.919681. eCollection 2022.

Abstract

OBJECTIVE

Graves' disease (GD) is an organ-specific autoimmune disease characterized by the production of thyroid-stimulating antibodies (TSAb). The newly discovered CD4 T helper cells, Th9 and Th17 lymphocytes, have been confirmed to be closely associated with a variety of immune diseases. However, relationships with the onset and development of GD remain unclear. The purpose of this study was to investigate the roles of Th9 and Th17 in the pathogenesis and prognosis of GD.

PATIENTS

We recruited 26 patients with newly diagnosed GD, 45 patients with GD in remission, and 20 healthy individuals.

MEASUREMENTS

Thyroid function and autoantibodies were evaluated using chemiluminescence immunoassays. Th9 and Th17 cells were analyzed using flow cytometry. The expression of Foxo1, IRF-4, RORc, IL-9, and IL-17 mRNA was examined using real-time PCR, and IL-9 and IL-17 protein levels were measured using enzyme-linked immunosorbent assay.

RESULTS

Th9, Th17, and characteristic cytokines IL-9 and IL-17 in the GD-untreated group were significantly higher than those in the control and remission groups. The above indexes significantly decreased in the remission group, with the levels in the TRAb remission group being similar to those in the normal group, while in the TRAb remission group, levels were differentially increased. TRAb titer was positively correlated with the levels of Th9, Th17, and their functional cytokines.

CONCLUSIONS

Th9 and Th17 cells may be involved in the pathogenesis and disease outcome of GD, which could provide a new direction for developing immunotherapy for patients with GD.

摘要

目的

格雷夫斯病(GD)是一种器官特异性自身免疫性疾病,其特征在于产生甲状腺刺激抗体(TSAb)。新发现的 CD4 T 辅助细胞 Th9 和 Th17 淋巴细胞已被证实与多种免疫性疾病密切相关。然而,它们与 GD 的发病和发展的关系尚不清楚。本研究旨在探讨 Th9 和 Th17 在 GD 发病机制和预后中的作用。

患者

我们招募了 26 例新诊断的 GD 患者、45 例 GD 缓解患者和 20 名健康对照者。

测量

使用化学发光免疫分析评估甲状腺功能和自身抗体。使用流式细胞术分析 Th9 和 Th17 细胞。使用实时 PCR 检测 Foxo1、IRF-4、RORc、IL-9 和 IL-17 mRNA 的表达,并使用酶联免疫吸附试验测量 IL-9 和 IL-17 蛋白水平。

结果

未经治疗的 GD 组的 Th9、Th17 和特征性细胞因子 IL-9 和 IL-17 明显高于对照组和缓解组。缓解组上述指标明显下降,TRAb 缓解组水平与正常组相似,而 TRAb 缓解组则不同程度升高。TRAb 滴度与 Th9、Th17 及其功能细胞因子水平呈正相关。

结论

Th9 和 Th17 细胞可能参与 GD 的发病机制和疾病结局,为 GD 患者的免疫治疗提供了新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d4a/9352852/5f67949f0423/fimmu-13-919681-g001.jpg

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