重症肌无力患者外周血FOXP3、TGF-β1的变化及其与血清AChR抗体的关系

Expression of FOXP3 and TGF-β1 in peripheral blood of myasthenia gravis patients and those correlation with anti-AChR antibodies

目的探讨MG患者外周血FOXP3、TGF-β1及AChR抗体三者之间的关系,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IgG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FOXP3mRNA、TGF-β1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。

Objective To explore the further pathogenesis of MG,the correlations among the expression of FOXP3 in peripheral blood mononuclear 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 MG,there are no different of the anti-AChR-IgG positive rate and concentation between ocular MG subgroup and general MG subgroup ; （4） Relative expression of FOXP3 mRNA in PBMNCs was positive correla- tion 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 correla- tion 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.