Antibody effector mechanisms in myasthenia gravis-Pathogenesis at the neuromuscular junction
Antibody effector mechanisms in myasthenia gravis-Pathogenesis at the neuromuscular junction
复制标题
DOI：
10.3109/08916930903555943
复制
发表时间：
2010-08-01
期刊：
影响因子：
3.5
通讯作者：
Losen, Mario
中科院分区：
文献类型：
--
作者：
Gomez, Alejandro M.;Van den Broeck, Joost;Losen, Mario
重症肌无力（MG）是由针对肌肉烟碱乙酰胆碱受体（AChR）或肌肉特异性酪氨酸激酶（MuSK）的自身抗体引起的自身免疫性疾病。这些自身抗体定义了疾病的两种不同亚型-AChR-MG和MuSK-MG。AChR和MuSK都在神经肌肉接头（NMJ）的突触后膜上表达，NMJ是肌肉的高度特化区域，专门用于接收和处理来自运动神经的信号。自身抗体与突触后膜的蛋白质结合导致神经肌肉传递受损和肌肉无力。人IgG 1和IgG 3亚类的促炎抗体调节AChR，引起补体激活，并吸引淋巴细胞;共同作用降低AChR和AChR相关蛋白的水平，并减少突触后折叠。在具有抗MuSK抗体的患者中，没有证据表明连接褶皱丢失，AChR密度也没有明显损失。抗MuSK抗体主要是IgG 4同种型，其抗炎活性在功能上不同于其他IgG亚类。此外，IgG 4经历称为Fab臂交换的翻译后修饰，其防止抗原的交联。提示MuSK-MG与AChR-MG的发病机制可能不同。本文就IgG亚类对突触结构和功能的影响作一综述。
Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that are either directed to the muscle nicotinic acetylcholine receptor (AChR) or to the muscle-specific tyrosine kinase (MuSK). These autoantibodies define two distinct subforms of the disease-AChR-MG and MuSK-MG. Both AChR and MuSK arc expressed on the postsynaptic membrane of the neuromuscular junction (NMJ), which is a highly specialized region of the muscle dedicated to receive and process signals from the motor nerve. Autoantibody binding to proteins of the postsynaptic membrane leads to impaired neuromuscular transmission and muscle weakness. Pro-inflammatory antibodies of the human IgG1 and IgG3 subclass modulate the AChR, cause complement activation, and attract lymphocytes; together acting to decrease levels of the AChR and AChR-associated proteins and to reduce postsynaptic folding. In patients with anti-MuSK antibodies, there is no evidence of loss of junctional folds and no apparent loss of AChR density. Anti-MuSK antibodies are predominantly of the IgG4 isotype, which functionally differs from other IgG subclasses in its anti-inflammatory activity. Moreover, IgG4 undergoes a posttranslational modification termed Fab arm exchange that prevents cross-linking of antigens. These findings suggest that MuSK-MG may be different in etiological and pathological mechanisms from AChR-MG. The effector functions of IgG subclasses on synapse structure and function are discussed in this review.