Muscle-specific kinase (MuSK) plays a critical role in establishing and maintaining neuromuscular synapses. Antibodies derived from immunizing animals with MuSK were important tools to help detect MuSK and its activity. The role of antibodies in MuSK-related research got an extra dimension when autoantibodies to MuSK were found to cause myasthenia gravis (MG) in 2001. Active immunization with MuSK or passive transfer of polyclonal purified IgG(4) fractions from patients reproduced myasthenic muscle weakness in a range of animal models. Polyclonal patient-purified autoantibodies were furthermore found to block agrin-Lrp4-MuSK signaling, explaining the synaptic disassembly, failure of neuromuscular transmission and ultimately muscle fatigue observed in vivo. MuSK autoantibodies are predominantly of the IgG4 subclass. Low levels of other subclass MuSK antibodies coexist, but their role in the pathogenesis is unclear. Patient-derived monoclonal antibodies revealed that MuSK antibody subclass and valency alters their functional effects and possibly their pathogenicity. Interestingly, recombinant functional bivalent MuSK antibodies might even have therapeutic potential for a variety of neuromuscular disorders, due to their agonistic nature on the MuSK signaling cascade. Thus, MuSK antibodies have proven to be helpful tools to study neuromuscular junction physiology, contributed to our understanding of the pathophysiology of MuSK MG and might be used to treat neuromuscular disorders. The source of MuSK antibodies and consequently their (mixed) polyclonal or monoclonal nature were important confounding factors in these experiments. Here we review the variety of MuSK antibodies described thus far, the insights they have given us and their potential for the future.

肌肉特异性激酶 (MuSK) 在建立和维持神经肌肉突触中起着关键作用。来自用 MuSK 免疫动物的抗体是帮助检测 MuSK 及其活性的重要工具。当 2001 年发现 MuSK 自身抗体导致重症肌无力 (MG) 时，抗体在 MuSK 相关研究中的作用得到了额外的重视。 MuSK 的主动免疫或患者多克隆纯化 IgG(4) 组分的被动转移再现了肌无力肌无力在一系列动物模型中。此外，还发现多克隆患者纯化的自身抗体可阻断 agrin-Lrp4-MuSK 信号传导，从而解释了在体内观察到的突触分解、神经肌肉传递失败和最终肌肉疲劳. MuSK 自身抗体主要是 IgG4 亚类。低水平的其他亚类 MuSK 抗体共存，但它们在发病机制中的作用尚不清楚。患者来源的单克隆抗体揭示了 MuSK 抗体的亚类和价态会改变它们的功能作用和可能的致病性。有趣的是，重组功能性二价 MuSK 抗体甚至可能对多种神经肌肉疾病具有治疗潜力，因为它们对 MuSK 信号级联具有激动作用。因此，MuSK 抗体已被证明是研究神经肌肉接头生理学的有用工具，有助于我们了解 MuSK MG 的病理生理学，并可用于治疗神经肌肉疾病。MuSK 抗体的来源及其（混合）多克隆或单克隆性质是这些实验中的重要混杂因素。在这里，我们回顾了迄今为止描述的各种 MuSK 抗体、它们为我们提供的见解以及它们对未来的潜力。