CD4^+CD25^+调节性T细胞与系统性红斑狼疮病情活动性关系的研究

Association between CD4^+CD25^+ regulative T cells and systemic lupus erythematosus disease active stage

目的:检测系统性红斑狼疮患者外周血CD4+CD25+、CD4+CD8+调节性T细胞亚群,探讨其与疾病活动性、肾脏损伤、血清抗ds-DNA抗体及免疫球蛋白和补体C3含量的关系。方法:采用流式细胞术检测北京协和医院住院和门诊SLE患者(n=37)外周血CD4+CD25+T、CD4+CD8+T细胞群比例,以15例RA和15例SS组成自身免疫性疾病对照,30例健康体检者作为正常对照,观察调节性T细胞亚群与SLE患者疾病活动性指标SLEDAI、IgG、C3及血清抗ds-DNA抗体的关系。结果:①疾病活动期SLE患者外周血CD4+CD25+调节性T细胞群比例显著低于正常对照组(P<0.01),疾病稳定期和风湿性疾病对照组与正常对照组结果差异无统计学意义。疾病活动期和稳定期SLE患者CD4+CD8+T细胞群比例都略高于正常对照组,但未发现结果差异有统计学意义(P>0.05)。②疾病活动期SLE患者外周血CD4+CD25+T细胞比例及CD4+CD25+/CD4+值显著低于稳定期患者(P<0.01)。SLE患者外周血CD4+CD25+/CD4+值与SLEDAI、补体C3呈低度相关(r分别为-0.491、0.368,P<0.05),CD4+CD25+T细胞数量与SLEDAI呈负相关(r=-0.578,P<0.05)。③SLE并发肾病组外周血CD4+CD25+T细胞群比例及CD4+CD25+/CD4+值显著低于非肾病组(P<0.01;P<0.05)。同一SLE患者治疗前后CD3+CD4-CD8-细胞和NK细胞降低,CD4+CD25+细胞、CD4+CD25+/CD4+值及CD8+T细胞增加,但未发现这些结果差异有统计学意义。本次研究未发现NK细胞、CD4+CD8+T细胞、CD4+CD25+T细胞群比例在ds-DNA+组与ds-DNA-组之间结果差异有统计学意义。结论:SLE患者外周血CD4+CD25+T细胞群比例与SLEDAI成负相关,与肾脏的损害也有密切关系,但与血清抗ds-DNA抗体产生的关系不明显。活动期SLE患者外周血CD4+CD25+T细胞减少,稳定期CD4+CD25+T细胞比例回升,因此推测CD4+CD25+T细胞的变化可能是导致疾病发生和病情发展及相关器官(如肾脏)损伤的关键环节之一。

Objective：To investigate the ratios of peripheral blood CD4^＋ CD25^＋ , CD4^＋ CD8^＋ regulative T ceils of systemic lupus erythematosus （SLE） patients, and explore the association with disease active stage, nephropathy, serum anti-ds-DNA antibody, and both IgG and C3 levels. Methods：The percentage of CD4^＋ CD25^＋ T cells and CD4^＋ CD8^＋ T cells of peripheral blood from patients with systemic lupus erythematosus（SLE）（30 females and 7 males）,30 rheumatism controls and 30 normal individuals were measured by floweytometry. Results：Patients with active disease had statisitically lower levels of CD4^＋ CD25^＋T cells than did normal controls（P 〈 0. 01 ） ,whereas no significance could be found between patients with non-active disease and normal controls. No significance could be found between rheumatism controls and normal controls. The percentage of peripheral blood CD4^＋ CD25^＋ T ceils in patients with active disease was significantly lower compared to patients with non-active disease（ P 〈 0. 01 ）, and those were related to the disease active stage. SLE patients with nephropethy still had significantly lower levels of CD4^＋ CD25 ^＋ T ceils and CD4^＋ CD25^＋/CD4^＋ than did patient without nephropothy （P 〈 0. 01 ）. No significance could be found among patients with ds-DNA - and ds-DNA^＋. After treated, the numbers of NK and CD3^＋ CD4^- CD8^- were found decresed, and CD8^＋ ,CD4^＋ CD25^＋ ,CD4^＋ CD25^＋/CD4^＋ incresed,but all these resuits were no statistical differences between pre-therapy and post-therapy. Conclusion：The decrease of peripheral blood CD4^＋CD25^＋ T cells in blood of patients with SLE is related to disease active stage and also associate with nephropethy. The decrese of CD4^＋ CD25^＋ T cells may play a crucial role in the pathogenesis of SLE.