系统性红斑狼疮初发患者Th细胞异常分化相关分子基因表达研究

Abnormal Th cell differentiation associated gene expression in systemic lupus erythematosus patients

目的 在研究系统性红斑狼疮 (SLE)患者存在Th1/Th2失衡与其调控细胞因子及其受体密切相关的基础上 ,探讨SLE患者在调控Th1/Th2分化的其他环节上也存在有基因表达的异常。方法 采用TaqManRealTimePCR的方法研究 38例初发SLE患者调控Th类细胞分化的细胞转录调控水平 (IκB、IRF 1、STAT 4、GATA 3、IL 4R)、细胞趋化、粘附和迁移有关的基因 (CCR1、CCR2、CCR4、CCR5 )、与细胞凋亡相关的基因 (caspase 1)、参与信号传导 (CD38)基因的表达 ,并以 2 8名正常人和 5 0例类风湿关节炎 (RA)患者作为对照。结果 ①与正常人比初发SLE患者调控向Th1分化的白细胞介素(IL) 12 /IL 12Rβ2 /STAT 4通路中STAT 4的表达水平并未见显著降低 ,反倒升高 (P <0 0 1) ;IRF 1的水平无明显改变 (P >0 0 5 ) :调控向Th2分化的IL 4 /IL 4R/GATA 3通路中GATA 3的表达降低 (P <0 0 1)。②以Th1占优势的RA患者中 ,调控向Th1方向分化的STAT 4的表达升高 (P <0 0 1) ,IRF 1表达却下降 (P <0 0 1) ;调控向Th2分化的IL 4R表达降低 (P <0 0 1) ,但GATA 3的表达却升高 (P <0 0 1) ,较初发SLE患者STAT 4升高 (P <0 0 1) ,IκB、IRF 1的基因表达水平降低 (P <0 0 1) ;GATA 3、IL 4R也升高 (P <0 0 1)。结论 在SLE患者中IL 12、

Objective To continue to study if there is any other pathogenic gene expression related to Th1/Th2 abnormal differentiation,based on the author′s previous results,which have shown that Th1/Th2 unbalance is due to the cytokines and cytokine receptors of differentiation.Methods TaqMan Real time PCR was used to detect the gene expression of Th1/Th2 control in recent onset systemic lupus erythematosus (SLE) patients ( n =38).The genes include IκB,IRF 1,STAT4,GATA3,IL 4R and the others such as CCR1,CCR2,CCR4,CCR5,caepase 1 and CD38,which participate in inflammation,cell apoptosis and so on.Rheumatoid arthritis (RA) patients ( n =50) and normal people ( n =28) were control groups.Results ① Resent onset SLE patients comparing to normal people:STAT4 expression in IL 2/IL 12R β 2/STAT4 access which induced Th1 differentiation increased significantly ( P <0 01);IRF 1 expression showed no significant change ( P >0 05) ;GATA3 expression which induced Th2 differentiation in IL 4/IL 4R/GATA3 access decreased significantly ( P <0 01).② Th1 dominated RA group comparing to normal people:STAT4 expression increased inverse IRF 1 expression decreased,occurring in Th1 induced differentiation ( P <0 01); IL 4R expression decreased inverse GATA3 expression increased,occurring in Th2 induced differentiation ( P <0 01);Th1 dominated RA group comparing to SLE patients:STAT4,GATA3 and IL 4R increased ( P <0 01),IκB and IRF 1 decreased ( P <0 01).③ CCR1,CCR2,CCR4 and CCR5 all increased significantly in RA group compared with normal people.Conclusion Abnormal IL 12,IL 18 and IL 12R regulation is possibly not the only reason of Th1/Th2 unbalance.Other regulatory access cannot be excluded and some suggested causation comprises STAT4,GATA3 phosphate and transposition;different gene expression exists in different disease stages;there is no significant Th1 or Th2 dominance in SLE patients and RA patients,referring to Th1/Th2 signal transduction level;CCR1,CCR2,CCR4 and CCR5 all increased in RA group.They may play an important role in RA.