Abstract

Background

Myasthenia gravis (MG) is an antibody-mediated, autoimmune neuromuscular disease. Reports have indicated that the CD28/B7 ligand interactions play a crucial role during primary immune responses. Hence, the aim of the present study was to investigate the possible effects of the CD28/B7 pathway on the occurrence and development of MG and its associated cytokine factors.

Methods

An experimental autoimmune myasthenia gravis (EAMG) was initially established by immunization of Lewis rats with acetylcholine receptor (AChR) α97-116 peptide. Then the rats were treated with dexamethasone and CTLA4-Ig (used for inhibiting the CD28/B7 pathway). Serum levels of AChR IgG and AChR IgG2b were then detected using ELISA. The clinical features, muscle contraction function, AChR content, expression of CD28, CTLA4, B7.1 and B7.2 in mononuclear cells of peripheral blood and the secretion of cytokines (INF-γ, IL-2, IL-10 and IL-12) in serum of rats were measured. Finally, lymphocyte proliferation upon CTLA4 IgG treatment was examined in vitro.

Results

Inhibition of the CD28/B7 pathway and dexamethasone were found to significantly improve clinical symptoms of EAMG rats, reduce serum levels of AChR IgG, AChR IgG2b, INF-γ, IL-2, IL-10 and IL-12, the expression of CD28, CTLA4, B7.1 and B7.2 in mononuclear cells of peripheral blood, and enhance muscle contraction function and AChR content in the muscle in vivo. Meanwhile, CTLA4 IgG could abolish the increased lymphocyte proliferation following AChR stimulation in vitro.

Conclusion

Overall, the suppression of the CD28/B7 pathway by CTLA4-Ig can have the potential to retard the occurrence and development of MG.

中文翻译：

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抑制CD28/B7通路可降低重症肌无力的发生和发展以及细胞因子水平

 抽象的

 背景

重症肌无力 (MG) 是一种抗体介导的自身免疫性神经肌肉疾病。报告表明 CD28/B7 配体相互作用在初次免疫反应中发挥着至关重要的作用。因此，本研究的目的是探讨CD28/B7通路对MG发生、发展及其相关细胞因子的可能影响。

 方法

实验性自身免疫性重症肌无力 (EAMG) 最初是通过用乙酰胆碱受体 (AChR) α97-116 肽免疫 Lewis 大鼠建立的。然后用地塞米松和CTLA4-Ig（用于抑制CD28/B7途径）治疗大鼠。然后使用 ELISA 检测 AChR IgG 和 AChR IgG2b 的血清水平。临床特征、肌肉收缩功能、AChR含量、外周血单个核细胞CD28、CTLA4、B7.1、B7.2的表达及细胞因子(INF-γ、IL-2、IL-10、IL-1)的分泌情况。 12) 测定大鼠血清中的含量。最后，在体外检查 CTLA4 IgG 处理后的淋巴细胞增殖情况。

 结果

抑制CD28/B7通路和地塞米松可显着改善EAMG大鼠的临床症状，降低血清AChR IgG、AChR IgG2b、INF-γ、IL-2、IL-10和IL-12的水平，降低CD28的表达。 、外周血单核细胞中的CTLA4、B7.1和B7.2，增强肌肉收缩功能和肌肉体内AChR含量。同时，CTLA4 IgG可以消除体外AChR刺激后增加的淋巴细胞增殖。

 结论

总体而言，CTLA4-Ig 对 CD28/B7 通路的抑制有可能延缓 MG 的发生和发展。