Objective The purpose of the current study is to demonstrate possible involvement of CD4+CD25+Treg cells and TGF-β in immune activation in patients with myasthema gravis(MG).If so,how does CD4+CD25+Treg cells and TGF-β,collaborate to impact on the production of pathogenic antiAChR antibodies(Ab)?Methods 40 MG in-patients with recent onset or deterioration and age and gender-matched 38 healthy subjects were consecutively enrolled.Flow cytometry was employed to detect circulating CD4+CD25+Treg cells.Levels of AChR-Abs and TGF-β1 in serum were detected by radioimmunoassay and enzyme-linked immunoabsorbance assay respectively.Resets Numbers of CD4+CD25+Treg cells were significanfly decreased in MG patients(3.0%±2.5%)compared with healthy controls(4.6%±3.7%,P=0.03).Decreased production of CD4+CD25+Treg cells was associated with late-onset,longer-duration,positive-MG sera for AChR-Abs,normal or atrophic thymus,and nonthymectomy treatment et al,respectively.Although CD4+CD25+Treg cells were not linear-correlated with serum anti-AChR Ab fiters,but were conversely correlated with each other in MG patients without thymona(non-MGT)(r=-0.37,P=0.02).Likewise,levels of TGF-β1 in 31 non-MGT patients(112 ng/L±83ng/L)were decreased compared with those of healthy subjects(215 ng/L ±134 ng/L,P=0.00),and was conversely correlated with titers of anti-AChR Abs(r=-0.37,P=0.02).The titer of anti-AChR Abs were correlated with Osserman classification and MGFA grade(r=0.34,P=0.03).Conclusion Nambers of CD4+CD25+Treg cells and levels of TGF-β1 in MG patients were significantly decreased compared with healthy controls,and may thus contribute to the pathogenesis of MG.Numbers of CD4+CD25+Treg cells were conversely correlated with levels of anti-AChR Abs in non-MGT patients.%目的 探讨重症肌无力(MG)患者外周血CD4+CD25+调节性T(Treg)细胞数量与血清抗乙酰胆碱受体抗体(AChR-Ab)和转化生长因子(TGF)-β1含量的相关性.方法 前瞻性地纳入40例新近发病或加重的MG住院患者和38名年龄、性别匹配的健康对照,应用流式细胞仪检测外周血CD4+ CD25+ Treg细胞数量,酶联免疫法检测血清TGF-β1含量,放免法检测血清AChR-Ab滴度,并对三者进行了相关性分析.结果 MG患者外周血CD4+CD25+Treg细胞百分率(3.0%±2.5%)显著低于健康对照(4.6%±3.7%,P=0.03).发病晚、病程长、抗AChR-Ab阳性、胸腺正常或退化以及未接受胸腺切除治疗等因素与MG患者CD4+CD25+Treg细胞减低有关.在31例非胸腺瘤MG(non-MGT)患者中,血清TGF-β1含量(112 ng/L±83 ng/L)显著低于健康对照(215 ng/L±134 ng/L,P=0.00),但在MG各临床亚型之间差异无统计学意义.虽然MG患者CD4+ CD25+Treg细胞百分率与血清AChR-Ab滴度不呈线性相关,但在非MGT患者中二者呈负相关(r=-0.37,P=0.02).非MGT患者血清AChR-Ab滴度还与Osserman临床分型和MGFA评分之间呈正相关(均r=0.34,P=0.03).非MGT患者血清TGF-β1含量与美国MG协会(MGFA)评分和CD4+CD25+Treg细胞百分率无相关性.结论 MG患者外周血CD4+CD25+Treg细胞百分率和血清TGF-β1含量均明显低于健康对照,可能参与了MG的发病.非MGT患者中Treg细胞百分率与AChR-Ab滴度呈负相关,检测其水平可能对评估MG病情及治疗提供理论依据,但是应用于临床还需要更多的相关研究.
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