重症肌无力患者外周血FOXP3、TGF-B1的变化及其与血清AChR抗体的关系

目的 探讨重症肌无力(MG)患者外周血叉头样转录因子P3(FOXP3)、转化生长因子-β1(TGF-β1)及乙酰胆碱受体抗体(AChR-Ab)三者之间的关系,揭示MG的发病机制.方法 利用RT-PCR技术检测41例MG患者和20例体检健康者外周血单个核细胞FOXP3 mRNA的表达,ELISA技术检测外周血清TGF-β1浓度、抗AChR抗体水平,分析三者之间的关系.结果 (1)FOXP3 mRNA的表达水平在MG患者组明显低于正常对照组(P<0.01),在25例眼肌型患者与16例全身型患者中的表达无差异性(P>0.05);(2)MG患者组外周血清TGF-β1浓度在MG患者组明显低于正常对照组(P<0.01),但在25例眼肌型患者与16例全身型患者中的表达无差异性(P>0.05);(3)41例MG患者中有30例患者血清中可检测出IgG型AChR抗体,其中眼肌型18例,全身型12例,两亚型的AChR抗体阳性率和抗体水平无显著差异(P>0.05);(4)各组外周静脉血单个核细胞FOXP3 mRNA的表达与血清TGF-β1浓度成正相关,相关系数为0.84(P<0.01);与lgG型AChR抗体水平呈负相关,相关系数为-0.77(P<0.01);血清TGF-β1浓度与IgG型AChR抗体水平呈负相关,-0.81(P<0.01).结论 FOXP3 mR-NA、TGF-B1低表达可能通过增加AChR抗体的产生,在MG的发病中起到重要作用.

Abstract：

Objective To explore the further pathogenesis of MG,the correlations among the expression of FOXP3 in peripheral blood mononuelear cells(PBMNCs) ,and the levels of TGF-β1 and anti-AChR bodies in serum of MG were analyzed. Methods The expressions of FOXP3 mRNA in PBMNCs from 40 MG patients and 20 healthy controls were detected by RT-PCR and the levels of TGF-β1 and anti-AChR antibodies in serum of MG group and HC were tested by ELISA,furthermore the relationships among them we analyzed. Results (1) The relative expression of FOXP3 mRNA in PBMNCs were significant lower in MG patiens group than that of health control group( P < 0. 01 ) ,while there is no different between 25 ocular MG patients and 16 general MG patients ( P > 0.05 ) ; ( 2 ) The levels of TGF-β1 in serum were significant lower in MG patients group than that of health control group(P <0. 01 ) ,while there is no different between 25 ocular MG patients and 16 general MG patients ( P > 0. 05 ) ; ( 3 ) From 41 MG patients, serum anti-AChR-IgG could detected in 30 patient including 18 ocular MG and 12 general M G, there are no different of the anti-AChR-IgG positive rate and coneentation between ocular MG subgroup and general MG subgroup ; (4) Relative expression of FOXP3 mRNA in PBMNCs was positive correlation with the level of TGF-β1 in serum of each group r = 0.84 ( P < 0. 01 ) , and negitive correlation with level of anti-AChR-IgG in serum of MG group r = -0.77(P <0.01 ) ;And in serum of MG group,the level of TGF-β1 was negatively correlation with the level of anti-AChR-IgG r = - 0.81( P < 0.01 ) . Conclusions Lower expression of FOXP3 mRNA in PBMNCs and TGF-β1 in peripheral blood may lead to more anti-AChR antibodies that cause MG.