[重症肌无力患者CD4+CD25+调节性T细胞数量、血清抗乙酰胆碱受体抗体水平与转化生长因子-β之间相关性的鉴定]
[Identification of correlations between numbers of CD4+ CD25+ Treg cells, levels of sera anti-AChR antibodies and transfer growth factor-beta in patients with myasthenia gravis].
作者信息
Wang Hua-bing, Zhang Jun-bao, Chui Li-ying
机构信息
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
出版信息
Zhonghua Yi Xue Za Zhi. 2008 Apr 15;88(15):1036-40.
OBJECTIVE
The purpose of the current study is to demonstrate possible involvement of CD4+ CD25+ Treg cells and TGF-beta in immune activation in patients with myasthenia gravis (MG). If so, how does CD4+ CD25+ Treg cells and TGF-beta, collaborate to impact on the production of pathogenic anti-AChR 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-beta1 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, positive-MG sera for AChR-Abs, normal or atrophic thymus, and non-thymectomy treatment et al, respectively. Although CD4+ CD25+ Treg cells 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-beta1 in 31 non-MGT patients (112 ng/L +/- 83 ng/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
Numbers of CD4+ CD25+ Treg cells and levels of TGF-beta1 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
本研究旨在证明重症肌无力（MG）患者中CD4+ CD25+调节性T细胞（Treg细胞）和转化生长因子-β（TGF-β）可能参与免疫激活。如果是这样，CD4+ CD25+ Treg细胞和TGF-β如何协同作用以影响致病性抗乙酰胆碱受体抗体（Ab）的产生？
方法
连续纳入40例近期发病或病情恶化的MG住院患者以及38例年龄和性别匹配的健康受试者。采用流式细胞术检测循环中的CD4+ CD25+ Treg细胞。分别通过放射免疫测定法和酶联免疫吸附测定法检测血清中乙酰胆碱受体抗体（AChR-Abs）和TGF-β1的水平。
结果
与健康对照（4.6%±3.7%，P = 0.03）相比，MG患者中CD4+ CD25+ Treg细胞数量显著减少（3.0%±2.5%）。CD4+ CD25+ Treg细胞产生减少分别与发病较晚、病程较长、AChR-Abs阳性MG血清、正常或萎缩胸腺以及非胸腺切除术治疗等因素相关。虽然在MG患者中CD4+ CD25+ Treg细胞与血清抗AChR抗体滴度无线性相关性，但在无胸腺瘤的MG患者（非MGT）中二者呈负相关（r = -0.37，P = 0.02）。同样，31例非MGT患者的TGF-β1水平（112 ng/L±83 ng/L）低于健康受试者（215 ng/L±134 ng/L，P = 0.00），且与抗AChR抗体滴度呈负相关（r = -0.37，P = 0.02）。抗AChR抗体滴度与Osserman分型和MGFA分级相关（r = 0.34，P = 0.03）。
结论
与健康对照相比，MG患者中CD4+ CD25+ Treg细胞数量和TGF-β1水平显著降低，可能因此参与MG的发病机制。在非MGT患者中，CD4+ CD25+ Treg细胞数量与抗AChR抗体水平呈负相关。
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