类风湿关节炎患者B细胞活化与磷脂酰肌3激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路相关性研究  

Correlation between B cell activation and PI3K/AKT/mTOR signaling pathway in patients with rheumatoid arthritis

作　　者：汪元[1] 黄传兵[1] 陈瑞莲[1] 王桂珍[1] 黄旦 林章英 潘慧 孙思凌 王露琳 WANG Yuan

机构地区：[1]安徽中医药大学第一附属医院,安徽合肥230031 [2]安徽中医药大学研究生院,安徽合肥230038

出　　处：《中医临床研究》2022年第20期13-16,共4页Clinical Journal Of Chinese Medicine

基　　金：新安医学教育部重点实验室开放基金项目(2020xayx01);安徽省高校优秀青年人才支持计划项目(gxyq2019031);国家临床重点专科中医风湿病科建设项目(财社[2013]239号);安徽省重点实验室建设项目(1306c083035);安徽省名中医刘健工作室建设项目(中医药发展秘[2018]11号);安徽省第12批“115”创新团队项目(皖人才办[2019]1号)。

摘　　要：目的:研究类风湿关节炎患者外周血B细胞活化与磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(Akt)/雷帕霉素靶蛋白(Mechanistic Target of Rapamycin Kinase,mTOR)信号通路的相关性。方法:选取符合诊断标准的类风湿关节炎患者30例和对照组20例健康人群纳入研究。采用流式细胞术检测B细胞绝对数目、B细胞百分比(Percentage of B cells,B%)、CD19^(+)CD81^(+)B细胞及CD19^(+)CD40^(+)B细胞表达水平,酶联免疫吸附试验法检测血清白细胞介素(Interleukin,IL)-1β、IL-2、IL-6、IL-10、PI3K、Akt、mTOR C1、3-磷酸肌醇依赖性蛋白激酶(Phosphoinositide-Dependent Protein Kinase,PDK)1、磷酸酶及张力蛋白同源物(Phosphatase And Tensin Homolog,PTEN)、抗环瓜氨酸多肽抗体的水平,常规检测类风湿因子、免疫球蛋白M、免疫球蛋白A、免疫球蛋白G、补体第三因子、补体第四因子、C-反应蛋白、红细胞沉降率水平,并收集同期临床资料。结果:与对照组相比,30例类风湿关节炎患者外周血中类风湿因子、抗环瓜氨酸多肽抗体、免疫球蛋白G、红细胞沉降率、C-反应蛋白水平均显著升高(P<0.01),全血中B细胞绝对数目、B%、CD19^(+)CD81^(+)B细胞及CD19^(+)CD40^(+)B细胞表达水平均显著升高(P<0.05或P<0.01),血清IL-1β、IL-2及IL-6水平显著升高(P<0.01),IL-10水平显著下降(P<0.01);30例类风湿关节炎患者外周血中PI3K、Akt、mTORC1和PDK1水平均显著升高(P<0.01);PTEN水平均显著下降(P<0.01)。相关性分析显示,类风湿关节炎患者B细胞绝对数目与类风湿因子、红细胞沉降率、C-反应蛋白、IL-1β、IL-2、PI3K、Akt、mTORC1、PDK1成正相关(P<0.05或P<0.01),与PTEN水平成负相关(P<0.01);B%与免疫球蛋白G、IL-6、Akt水平成正相关(P<0.01);CD19^(+)CD81^(+)B细胞的表达水平与IL-2、IL-6、PI3K、mTORC1水平成正相关(P<0.05或P<0.01);CD19^(+)CD40^(+)B细胞的表达水平与类风湿因子、IL-1β、PI3K、PDK1水平成正Objective:To study the correlation between peripheral blood B cell activation and PI3K/Akt/mTOR signaling pathway in patients with rheumatoid arthritis(RA).Methods:Thirty RA patients who met the diagnostic criteria and 20 healthy controls were selected.Flow cytometry was used to detect the absolute number of B cells(B),B%,CD19^(+)CD81^(+)B cells and CD19^(+)CD40^(+)B cell expression levels,and ELISA was used to detect serum IL-1β,IL-2,IL-6,IL-10,PI3K,Akt,mTORC1,PDK1,PTEN,anti-CCP antibody levels,RF,IgM,IgA,IgG,C3,C4,CRP,ESR levels were routinely detected,and clinical data during the same period was collected.Results:Compared with the control group,the levels of RF,anti-CCP antibody,IgG,ESR,and CRP in peripheral blood of 30 RA patients were significantly increased(P<0.01).The expression levels of B cells,B%,CD19^(+)CD81^(+)B cells and CD19^(+)CD40^(+)B cells were significantly increased(P<0.05 or P<0.01),and the levels of serum IL-1β,IL-2 and IL-6 were significantly increased(P<0.01).The level of IL-10 was decreased significantly(P<0.01);the levels of PI3K,Akt,mTORC1 and PDK1 in peripheral blood of 30 RA patients were significantly increased(P<0.01);the levels of PTEN were significantly decreased(P<0.01).Correlation analysis showed that the absolute number of B cells in RA patients was positively correlated with RF,ESR,CRP,IL-1β,IL-2,PI3K,Akt,mTORC1,PDK1 levels(P<0.05 or P<0.01),and negatively correlated with PTEN level correlation(P<0.01);B%was positively correlated with the levels of IgG,IL-6,and Akt(P<0.01).The expression level of CD19^(+)CD81^(+)B cells was positively correlated with the levels of IL-2,IL-6,PI3K,and mTORC1(P<0.05 or P<0.01);the expression level of CD19^(+)CD40^(+)B cells was positively correlated with the levels of RF,IL-1β,PI3K and PDK1levels(P<0.05 or P<0.01),and negatively correlated with the level of PTEN(P<0.05).Conclusion:There is abnormal activation of B cells in RA patients,and the abnormal activation mechanism may be related to the activation of PI3K/Akt/mTORC signaling pathway an

关 键 词：类风湿关节炎 B细胞活化 磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素靶蛋白 炎症因子 

分 类 号：R593.22[医药卫生—内科学]