Graves病外周血CD4^(+)T细胞ICOS及CD19^(+)B细胞ICOSL高表达且与促甲状腺素受体抗体(TRAb)水平正相关  

High expression of ICOS on CD4^(+)T cells and ICOSL on CD19^(+)B cells in peripheral blood and its positive correlation with TRAb in Graves’disease

作　　者：陈欣欣 王凤鸣 从相国[1] 沈琼[1] 陈蕾[1] CHEN Xinxin;WANG Fengming;CONG Xiangguo;SHEN Qiong;CHEN Lei(Department of Endocrinology,Suzhou Municipal Hospital Affiliated to Nanjing Medical University,Suzhou 215002,China)

机构地区：[1]南京医科大学附属苏州医院内分泌科,江苏苏州215002

出　　处：《细胞与分子免疫学杂志》2020年第12期1102-1108,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81900714);苏州市科技局民生科技(SYSD2019126)。

摘　　要：目的探索诱导性共刺激分子及配体(ICOS/ICOSL)在Graves病(GD)外周血淋巴细胞上的表达及临床意义。方法募集105例初发未治疗的GD甲亢患者纳入初发GD甲亢组,匹配同时期性别、年龄无差异的健康对照组67例。其中初发GD甲亢组有19例患者接受抗甲状腺药物治疗并在门诊规律随访直至TRAb转阴,以动态观察ICOS、ICOSL在治疗前后的变化。分离初发GD甲亢患者外周血单个核细胞(PBMC),PCR检测PBMC上ICOS、ICOSL mRNA的表达;流式细胞术分别检测CD4^(+)T细胞、CD8^(+)T细胞亚群表面ICOS及CD19^(+)B淋巴细胞表面ICOSL的表达,分析其与甲状腺功能及促甲状腺素受体抗体(TRAb)水平的相关性。动态观察GD甲亢患者治疗前后ICOS、ICOSL表达的变化。结果与健康对照组相比,初发GD甲亢组PBMC上ICOS及ICOSL mRNA表达水平均显著增加。初发GD甲亢组CD4^(+)T细胞表面ICOS表达水平升高,且与游离甲状腺三碘原氨酸(FT3)水平显著正相关;TRAb高滴度组CD19+B细胞表面ICOSL表达水平显著高于TRAb低滴度组;GD甲亢患者TRAb转阴后,CD4^(+)T细胞表面ICOS及CD19+B细胞表面ICOSL的表达水平较初发时显著下降。结论Graves病患者外周血CD4^(+)T细胞表面ICOS及CD19+B细胞表面ICOSL表达水平显著升高;随着TRAb水平降低,CD4^(+)T细胞表面ICOS及CD19+B细胞表面ICOSL表达水平有所恢复。Objective To detect the expression of inducible co-stimulator and inducible co-stimulator ligand(ICOS/ICOSL)on peripheral lymphocytes in patients with Graves’disease(GD)and its clinical significance.Methods A total of 105 untreated GD patients and 67 healthy controls were enrolled in our study.19 GD patients treated with anti-thyroid drugs were followed up in the outpatient department until TRAb were negative.The peripheral blood mononuclear cells(PBMCs)were separated and analyzed with PCR.ICOS expression on CD4^(+)/CD8^(+)T cells and ICOSL expression on CD19^(+)B cells were detected by flow cytometry.The correlations between the expression of ICOS/ICOSL with thyroid parameters and TRAb were analyzed.Results The expression of both ICOS and ICOSL mRNA in PBMCs of the untreated GD patients were significantly higher than those in the healthy controls.Compared with healthy controls,ICOS expression on CD4^(+)T cells and ICOSL expression on CD19^(+)B cells were up-regulated significantly in the GD patients.Correlation analysis showed that ICOS expression on CD4^(+)T cells was positively correlated with the level of free triiodothyronine(FT3)in the GD patients.In the group of GD patients with high TRAb titers in serum,ICOSL expression on CD19^(+)B cells notably increased as compared with that in the patients with low TRAb.ICOS expression on CD4^(+)T cells and ICOSL expression on CD19^(+)B cells were recovered in the GD patients with negative TRAb.Conclusion The expression of ICOS on the surface of CD4^(+)T cells and ICOSL on CD19^(+)B cells in peripheral blood of patients with Graves’s disease are significantly increased.With the decrease of TRAb level,the expression levels of ICOS on the surface of CD4^(+)T cells and ICOSL on CD19^(+)B cells are restored.

关 键 词：诱导性共刺激分子(ICOS) 诱导性共刺激分子配体(ICOSL) 促甲状腺素受体抗体(TRAb) GRAVES病 

分 类 号：R322.51[医药卫生—人体解剖和组织胚胎学] R593.2[医药卫生—基础医学]