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甲状腺相关性眼病患者外周血CD4+、CD8+T细胞百分比及细胞表面程序性死亡蛋白1表达的改变及其意义
夏晓玲,汤玮,孙亮亮,倪奇,刘浩琪,陆晓敏,孙政,石勇铨
0
(第二军医大学长征医院内分泌科, 甲状腺相关眼病诊治中心, 上海 200003
*通信作者)
摘要:
目的 观察甲状腺相关性眼病(TAO)患者外周血单个核细胞(PBMC)中CD4+、CD8+T细胞百分比及细胞表面程序性死亡蛋白1(PD-1)的表达水平,探索这两者变化在TAO发病机制及疾病诊断中的意义。方法 收集21例TAO患者、21例Graves病(GD)无眼病患者及20例健康对照者资料,采用流式细胞术检测所有受试者PBMC中CD4+、CD8+T细胞百分比及其表面PD-1的表达率,比较组间差异,分析其与患者病程、甲状腺功能、甲状腺相关抗体及TAO疾病活动性和严重程度之间的关系。结果 (1) TAO患者PBMC中CD4+、CD8+T细胞百分比分别为(35.9±14.5)%、(22.2±8.4)%,GD患者分别为(33.1±13.0)%、(18.6±9.2)%,均高于健康对照者[(17.4±7.4)%、(7.7±4.8)%,P<0.01]。(2) TAO及GD患者PBMC中CD4+T细胞表面PD-1表达率分别为(8.3±6.4)%、(28.0±26.6)%,均低于健康对照者[(52.2±28.6)%,P<0.01, P<0.05],且TAO患者低于GD患者(P<0.05);TAO患者PBMC中CD8+T细胞表面PD-1表达率低于健康对照者[(12.7±13.4)% vs (38.2±24.2)%,P<0.01]。(3) TAO患者PBMC中CD8+T细胞百分比与病程呈正相关(r=0.478,P<0.05)。(4) TAO患者活动期组与非活动期组、轻度组与中重度组间CD4+、CD8+T细胞百分比及其表面PD-1表达率差异均无统计学意义(P>0.05)。结论 TAO患者PBMC中CD4+、CD8+T细胞百分比及细胞表面PD-1表达存在异常,可能参与TAO的自身免疫过程。
关键词:  甲状腺相关性眼病  Graves眼病  程序性死亡蛋白1  共刺激分子  自身免疫
DOI:10.16781/j.0258-879x.2016.06.0704
投稿时间:2016-02-18修订日期:2016-03-23
基金项目:国家自然科学基金面上项目(81170728).
Changes of CD4+, CD8+ T cell proportions and cell surface programmed death-1 level in peripheral blood mononuclear cells of patients with thyroid-associated ophthalmopathy
XIA Xiao-ling,TANG Wei,SUN Liang-liang,NI Qi,LIU Hao-qi,LU Xiao-min,SUN Zheng,SHI Yong-quan
(Department of Endocrinology, Diagnosis and Treatment Center of Thyroid-Associated Ophthalmopathy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*Corresponding author)
Abstract:
Objective To observe the changes of CD4+, CD8+T cell proportions and the level of cell surface programmed death-1 (PD-1) in the peripheral blood mononuclear cells (PBMC) of patients with thyroid-associated ophthalmopathy (TAO), and to explore their roles in the pathogenesis and diagnosis of TAO. Methods The clinical data of 21 TAO patients, 21 Graves disease (GD) patients without ophthalmopathy and 20 healthy volunteers were collected. The proportions of CD4+, CD8+T cells in PBMCs and cell surface PD-1 expressions were tested by flow cytometry and were compared between different groups; and their correlation with disease course, thyroid functions, thyroid associated antibodies and severity of TAO were analyzed. Results (1)The proportions of CD4+, CD8+T cells in PBMCs of TAO patients ([35.9±14.5]% and [22.2±8.4]%, respectively) and GD patients ([33.1±13.0]% and [18.6±9.2]%, respectively) were both significantly higher than those in the healthy volunteers ([17.4±7.4]% and [7.7±4.8]% respectively, both P<0.01). (2) The expression of PD-1 on CD4+T cells in TAO and GD patients were (8.3±6.4)% and (28.0±26.6)%, respectively, with both being significantly lower than those in the healthy volunteers ([52.2±28.6]%, P<0.01 and P<0.05, respectively), and that in TAO patients was significantly lower than that in GD patients (P<0.05). The expression of PD-1 in CD8+T cells was significantly lower in TAO patients than that in the healthy volunteers ([12.7±13.4]% vs [38.2±24.2]%, P<0.01). (3) Correlation analysis showed that there was a positive correlation between disease course and CD8+T cell proportion in PBMCs of TAO patients (r=0.478, P<0.05). (4) There was no significant difference in CD4+,CD8+T cells proportions or their PD-1 expressions between active and inactive, mild and moderate-to-severe TAO patients (P>0.05). Conclusion The aberrant proportions of CD4+, CD8+T cells in PBMCs and cell surface PD-1 expression may participate in the autoimmune process of TAO.
Key words:  thyroid-associated ophthalmopathy  Graves ophthalmopathy  programmed death-1  costimulatory molecules  autoimmunity