摘要
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(112ng/L±83ng/L)显著低于健康对照(215ng/L±134ng/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—Ah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。
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 myasthenia gravis (MG). If so, how does CD4^+CD25^+ Treg cells and TGF-β, collaborate to impact on the production of pathogenic anti- AChR antibodies (Ab).9 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. Results Numbers of CD4^+CD25^+ Treg cells were significantly 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, pesitive-MG sera for AChR-Abs, normal or atrophic thymus, and nonthymectomy treatment et al, respectively. Although CD4^+CD25^+ Treg ceils were not linear-correlated with serum anti-AChR Ab titers, but were conversely correlated with each other in MG patients without thymoma (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 =1= 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 Numbers 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.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2008年第15期1036-1040,共5页
National Medical Journal of China