摘要
目的 观察自身免疫病(AID)患者外周血辅助性T细胞17(Th17)和调节性T细胞(Treg)的变化并探讨其意义.方法 回顾性分析了13 937例AID患者及267名健康者外周血Th17 和Treg细胞的绝对计数及Th17和Treg细胞的比值,这些AID患者包括类风湿关节炎(RA),系统性红斑狼疮(SLE)、原发性干燥综合征(pSS)、未分化脊柱关节病(USpA)、强直性脊柱炎(AS)、银屑病关节炎(PsA)、白塞综合征(BD)、肌炎、系统性硬化病(SSc)、混合性结缔组织病(MCTD)、血管炎和痛风患者.用流式细胞术检测受试者外周血Th17 和Treg细胞的绝对计数.采用t检验比较各组患者与健康对照组的Th17和Treg细胞绝对计数的差异.结果 与健康对照组相比,AID患者的Treg细胞水平明显偏低[(33.3±12.6)个/μl与(24.4±13.6)个/μl,t=10.540,P<0.001],Th17/Treg显著升高[(0.26±0.14)与(0.50±0.52),t=-23.599,P<0.001].其中,USpA[(10.6±8.8)个/μl,t=-5.515,P<0.001]、AS[(10.9±8.5)个/μl,t=-6.882,P<0.001]和痛风[(11.7±10.1)个/μl,t=-3.500,P=0.001]患者的Th17 细胞高于健康对照组[(8.1±4.1)个/μl],RA[(26.4±13.8)个/μl,t=7.835,P<0.001]、SLE[(16.9±12.6)个/μl,t= 18.583,P<0.001]、pSS[(25.4±15.1)个/μl,t=8.601,P<0.001]、USpA[(25.3±14.3)个/μl,t=7.757,P<0.001]、AS[(27.8±14.8)个/μl,t=5.843,P<0.001]、BD[(24.1±13.7)个/μl,t=7.519,P<0.001]、肌炎[(22.1±14.6)个/μl,t=9.934,P<0.001]、SSc[(25.6±15.1)个/μl,t=4.559,P<0.001]、MCTD[(20.1±11.9)个/μl,t=9.040,P<0.001]、血管炎[(24.1±14.9)个/μl,t=6.771,P<0.001]和痛风[(27.8±15.2)个/μl,t=3.271,P=0.001]患者的Treg细胞明显低于健康对照组[(33.3±12.6)个/μl].结论 在AID患者中,Th17细胞的绝对值高低不一,Treg细胞的绝对值几乎均低于正常,Th17/Treg细胞水平显著升高,提示AID的免疫失衡可能主要是由Treg细胞不足所致的自身免疫耐受缺陷导致.促进Treg细胞增殖,改善Treg细胞功能,诱导和恢复患者自身免疫耐受的免疫调节策略,有望为AID的治疗提供新的思路.
Abstract
Objective This study aims to observe changes in peripheral blood helper T cell 17(Th17)and regulatory T cell(Treg)levels in patients with autoimmune diseases(AID)and explore their significance.Methods A retrospective analysis was conducted on peripheral blood Th17 and Treg absolute counts,as well as the Th17/Treg ratio,in 13,937 AID patients and 267 healthy individuals.AID patients included those with rheumatoid arthritis(RA),systemic lupus erythematosus(SLE),primary Sjögren's syndrome(pSS),undifferentiated spondyloarthritis(USpA),ankylosing spondylitis(AS),psoriatic arthritis(PsA),Behçet's disease(BD),myositis,systemic sclerosis(SSc),mixed connective tissue disease(MCTD),vasculitis,and gout.Flow cytometry was used to detect Th17 and Treg absolute counts in the peripheral blood of the subjects.T-tests were employed to compare the differences in Th17 and Treg absolute counts between each patient group and the AID group,with P<0.05 considered statistically significant.Results Compared to the healthy control group,AID patients exhibited significantly lower levels of Treg cells[(33.3±12.6)cells/μl vs.(24.4±13.6)cells/μl,t=10.540,P<0.001]and a significantly elevated Th17/Treg ratio[(0.26±0.14)vs.(0.50±0.52),t=-23.599,P<0.001].Specifically,Th17 cell counts were higher in patients with USpA[(10.6±8.8)cells/μl,t=-5.515,P<0.001],AS[(10.9±8.5)cells/μl,t=-6.882,P<0.001],and gout[(11.7±10.1)cells/μl,t=-3.500,P=0.001]compared to the healthy control group[(8.1±4.1)cells/μl].Treg cell counts were significantly lower in patients with RA[(26.4±13.8)cells/μl,t=7.835,P<0.001],SLE[(16.9±12.6)cells/μl,t=18.583,P<0.001],pSS[(25.4±15.1)cells/μl,t=8.601,P<0.001],USpA[(25.3±14.3)cells/μl,t=7.757,P<0.001],AS[(27.8±14.8)cells/μl,t=5.843,P<0.001],BD[(24.1±13.7)cells/μl,t=7.519,P<0.001],myositis[(22.1±14.6)cells/μl,t=9.934,P<0.001],SSc[(25.6±15.1)cells/μl,t=4.559,P<0.001],MCTD[(20.1±11.9)cells/μl,t=9.040,P<0.001],vasculitis[(24.1±14.9)cells/μl,t=6.771,P<0.001],and gout[(27.8±15.2)cells/μl,t=3.271,P=0.001]compared to the healthy control group[(33.3±12.6)cells/μl].Conclusion In patients with AID,Th17 cell levels varied,while Treg cell levels were consistently lower than normal,leading to a significantly elevated Th17/Treg ratio.This suggests that immune imbalance in AID may be primarily attributed to deficient Treg cells,resulting in autoimmune tolerance defects.Strategies aimed at promoting Treg cell proliferation,improving Treg cell function,and inducing/recovering immune tolerance offer promising avenues for the treatment of AID.
基金项目
国家自然科学基金(82001740)
山西省基础研究计划项目(202203021221269)
NETL
NSTL
万方数据