Th1/Th2、CD28、ICOS、PD-1和CTLA-4在桥本甲状腺炎患者外周血中的表达及与甲状腺相关实验室指标的相关性

Expression of Th1/Th2,CD28,ICOS,PD-1 and CTLA-4 in peripheral blood of patients with Hashimoto′s thyroiditis and their correlations with thyroid related laboratory indicators

目的探讨辅助性T淋巴细胞1与辅助性T淋巴细胞2比值(Th1/Th2)、CD28、可诱导共刺激分子(ICOS)、程序性死亡受体1(PD-1)和细胞毒性T淋巴细胞相关抗原4(CTLA-4)在桥本甲状腺炎(HT)患者外周血中的表达及与甲状腺相关实验室指标的相关性。方法收集2021年在该院门诊或住院治疗的HT患者40例为HT组,另选择同期健康体检者40例为对照组。采用全自动化学发光免疫分析仪检测血清甲状腺过氧化物酶抗体(TPOAb)、促甲状腺激素(TSH)、游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)水平,采用酶联免疫吸附试验检测血清γ干扰素(IFN-γ)、白细胞介素(IL)-2、IL-4和IL-10水平,采用流式细胞仪检测外周血中Th1与Th2细胞,以及CD3^(+)CD4^(+)T淋巴细胞表面共信号分子CD28、ICOS、PD-1、CTLA-4水平。结果HT组血清FT4和TPOAb水平均明显高于对照组,TSH、FT3水平明显低于对照组,差异有统计学意义(P<0.05)。HT组外周血中Th1细胞及其相关细胞因子IFN-γ和IL-2水平,以及Th1/Th2明显高于对照组,差异有统计学意义(P<0.05)。HT组外周血CD3^(+)CD4^(+)T淋巴细胞表面CD28、ICOS和PD-1水平明显高于对照组,差异有统计学意义(P<0.05);两组CTLA-4水平比较,差异无统计学意义(P>0.05)。FT4水平与Th1细胞、Th1/Th2水平呈正相关(P<0.05);TSH水平与Th1细胞、Th1/Th2和IL-2水平呈负相关(P<0.05);TPOAb水平与Th1细胞、Th1/Th2、IFN-γ、IL-2、CD28及ICOS水平呈正相关(P<0.05)。结论HT患者外周血中Th1细胞及其相关细胞因子IFN-γ和IL-2水平较健康体检者均明显上调,其CD3^(+)CD4^(+)T淋巴细胞表面CD28、ICOS和PD-1的表达也均明显上调。Th1细胞及其相关细胞因子,以及CD28、ICOS和PD-1可能在HT的发病机制中发挥了重要作用。

Objective To investigate the expression of helper T lymphocyte 1 to helper T lymphocyte 2 ratio(Th1/Th2),CD28,inducible co-stimulator(ICOS),programmed death receptor 1(PD-1)and cytotoxic T lymphocyte associated antigen 4(CTLA-4)in peripheral blood of patients with Hashimoto′s thyroiditis(HT)and their correlations with thyroid related laboratory indicators.Methods A total of 40 patients with HT who were treated in the outpatient or inpatient department of the hospital in 2021 were collected as the HT group,and 40 healthy patients with physical examination in the same period were selected as the control group.Serum thyroid peroxidase antibody(TPOAb),thyroid stimulating hormone(TSH),free throxine(FT4),free triiodothyronine(FT3)levels were detected by automatic chemiluminescence immunoassay.Serum interferonγ(IFN-γ),interleukin(IL)-2,IL-4 and IL-10 levels were detected by enzyme-linked immunosorbent assay.The levels of peripheral blood Th1,Th2 cells and CD3^(+)CD4^(+)T lymphocytes surface co-signal molecules CD28,ICOS,PD-1 and CTLA-4 were detected by flow cytometry.Results The levels of serum FT4 and TPOAb in HT group were significantly higher than those in control group,while the levels of TSH and FT3 in HT group were significantly lower than those in control group,the differences were statistically significant(P<0.05).The levels of Th1 cells and related cytokines IFN-γ,IL-2 and Th1/Th2 in peripheral blood in HT group were significantly higher than those in control group,the differences were statistically significant(P<0.05).The levels of CD28,ICOS and PD-1 on peripheral blood CD3^(+)CD4^(+)T lymphocytes surface in HT group were significantly higher than those in control group,the differences were statistically significant(P<0.05).There was no significant difference on CTLA-4 level between the two groups(P>0.05).FT4 level correlated positively with Th1 cells and Th1/Th2 levels(P<0.05).TSH level correlated negatively with Th1 cells,Th1/Th2 and IL-2 levels(P<0.05).TPOAb levels correlated positively with Th1 cells,Th1/Th2,IFN-γ,IL-2,CD28 and ICOS levels(P<0.05).Conclusion The levels of Th1 cells and its related cytokines IFN-γand IL-2 in peripheral blood of HT patients up-regulate significantly compared with those of healthy subjects,and the expressions of CD28,ICOS and PD-1 on CD3^(+)CD4^(+)T lymphocytes surface also up-regulate significantly.Th1 cells and their related cytokines,as well as CD28,ICOS and PD-1 might play an important role in the pathogenesis of HT.