初发Graves病患者外周血调节性T细胞及滤泡调节性T细胞检测的临床研究

Clinical study on regulatory T cells and follicular regulatory T cells detection of peripheral blood in patients with newly-diagnosed Graves' disease

摘要:

目的： 检测Graves病（Graves' disease，GD）患者外周血调节性T细胞（regulatory T cells，Tregs）、滤泡调节性T细胞（follicular regulatory T cells，Tfrs）、滤泡辅助性T细胞（follicular helper T cells，Tfhs）数量及其表面分子肿瘤坏死因子受体超家族成员4（tumor necrosis factor receptor superfamily member 4，OX40）、程序性死亡因子1（programmed-death 1，PD-1）的表达。方法： 纳入初发GD患者23例（GD组）和健康对照者22例（NC组），通过流式细胞术检测2组外周血Tregs（CD3⁺CD4⁺CD25⁺Foxp3⁺）、Tfrs（CD4⁺Foxp3⁺PD-1⁺CXCR5⁺）及Tfhs（CD4⁺Foxp3^-PD-1⁺CXCR5⁺）细胞比例及其表面分子OX40、PD-1表达，分析GD发病与Tregs、Tfrs、Tfhs及其OX40、PD-1表达的关系，同时分析各检测指标与临床指标的相关性，初步探讨其临床意义。结果： 与NC组相比，GD组Tregs数量明显升高，Tregs上PD-1表达降低，Tregs上PD-1表达与TRAb水平呈显著负相关；初发GD患者Tfrs数量明显降低，且Tfrs上OX40表达上调，Tfrs数量与TRAb呈显著负相关。结论： PD-1在Tregs上的低表达可能通过影响Tregs功能参与GD发病，GD患者体内Tfrs数量明显减少，且其OX40表达明显升高，OX40可能通过影响Tfrs与Tfhs稳态参与GD发病，这为临床上关于GD的治疗提供了新思路。

Abstract:

Objective: To detect the number of regulatory T cells (Tregs) , follicular regulatory T cells (Tfrs) , follicular helper T cells (Tfhs) , and the expression of their surface molecules tumor necrosis factor receptor superfamily member 4 (OX40) and programmed-death factor 1 (PD-1) in peripheral blood of patients with Graves' disease (GD) . Methods: A total of 23 newly-diagnosed GD patients (GD group) and 22 normal controls (NC group) were enrolled in this study. The proportions of Tregs (CD3⁺CD4⁺CD25⁺Foxp3⁺) , Tfrs (CD4⁺Foxp3⁺PD-1⁺CXCR5⁺) and Tfhs (CD4⁺Foxp3^-PD-1⁺CXCR5⁺) , and the expression of their surface molecules OX40 and PD-1 in peripheral blood of the two groups were detected by flow cytometry. The relationship between the pathogenesis of GD and Tregs, Tfrs, Tfhs, OX40 and PD-1 was analyzed. The correlations between the detection indexes and clinical indexes were also analyzed, and the clinical significance was preliminarily discussed. Results: Compared with the NC group, the number of Tregs in the GD group was significantly increased, and the expression of PD-1 on Tregs was decreased. PD-1 expression on Tregs was significantly negatively correlated with TRAb level. The number of Tfrs was significantly decreased in newly-diagnosed GD patients, and OX40 expression was up-regulated on Tfrs. The number of Tfrs was negatively correlated with TRAb. Conclusion: The low expression of PD-1 on Tregs may be involved in the pathogenesis of GD by affecting the function of Tregs. The number of Tfrs in GD patients is significantly reduced, and the expression of OX40 is significantly increased. OX40 may be involved in the pathogenesis of GD by affecting Tfrs and Tfhs homeostasis. These results may provide some new ideas for the clinical treatment of GD.