MuSK重症肌无力：从抗原抗体到临床翻译
MuSK myasthenia gravis: from antigen-antibody to clinical translation.
摘要(中文译文)
抗MuSK抗体阳性重症肌无力（MuSK-MG）以严重且可能危及生命的肌无力为特征。抗MuSK抗体是该病的关键致病驱动因素。本综述全面总结了当前关于MuSK及其在MuSK-MG中作用的认识的最新进展。MuSK是一种受体酪氨酸激酶，在神经肌肉接头处至关重要，其在该处形成集聚蛋白-LRP4-MuSK三联功能复合物，启动并维持集聚蛋白诱导的突触后膜乙酰胆碱受体聚集。尽管抗MuSK抗体涵盖所有IgG亚类（IgG1-4），但IgG4是主要的致病亚类。IgG4抗体经历Fab臂交换，获得功能性单价性；这种单价IgG4破坏LRP4-MuSK相互作用，从而阻断下游信号传导并促发肌无力症状。新出现的证据表明，IgG1-3抗MuSK抗体也具有致病性，尽管某些克隆对MuSK磷酸化表现出激动效应。此外，本综述审视了该病的各种诊断方法并权衡其优缺点。MuSK蛋白及其自身抗体对诊断和治疗均至关重要。本文讨论了放射免疫沉淀法和酶联免疫吸附试验及其优势与局限性，并指出基于细胞的检测具有高准确性。抗MuSK抗体检测是金标准诊断生物标志物。最后，本综述涵盖了MuSK-MG的各种治疗策略，包括免疫抑制剂、单克隆抗体、CAR-T细胞疗法和新生儿Fc受体阻断。B细胞靶向疗法（如抗CD20单克隆抗体）和MuSK激动剂代表了MuSK-MG未来有前景的治疗策略。总体而言，本综述对MuSK-MG诊断和治疗的当前实践及未来策略提供了明确的总结，为进一步研究 laying out 清晰的标志，以增强我们对这一疾病的理解。
Abstract
Anti-MuSK antibody-positive myasthenia gravis (MuSK-MG) is characterized by severe and potentially life-threatening weakness. Anti-MuSK antibodies are key pathogenic drivers of this disorder. This review provides a comprehensive summary of the current state-of-the-art with respect to the understanding of MuSK and its role in MuSK-MG. MuSK, a receptor tyrosine kinase, is essential at the neuromuscular junction, where it forms an agrin-LRP4-MuSK tripartite functional complex that initiates and maintains agrin-induced acetylcholine receptor clustering at the postsynaptic membrane. Although anti-MuSK antibodies encompass all IgG subclasses (IgG1-4), IgG4 is the predominant pathogenic subclass. , IgG4 antibodies undergo Fab-arm exchange, acquiring functional monovalency; this monovalent IgG4 disrupts LRP4-MuSK interactions, thereby blocking downstream signaling and precipitating myasthenic symptoms. Emerging evidence indicates that IgG1-3 anti-MuSK antibodies are also pathogenic, although some clones exhibit agonistic effects on MuSK phosphorylation. Further, this review examines the various diagnostic methods for this condition and weighs the advantages and disadvantages. Both MuSK protein and its autoantibodies are pivotal for diagnosis and therapy. Radioimmunoprecipitation assays and enzyme-linked immunosorbent assays and their benefits ad limitations are discussed, and cell-based assays are noted for their high accuracy. Anti-MuSK antibody testing is the gold standard diagnostic biomarker. Finally, the review covers the various therapeutic strategies for MuSK-MG, including immunosuppressants, monoclonal antibodies, CAR-T cell therapy, and neonatal Fc receptor blockade. B-cell-targeted therapies (e.g., anti-CD20 monoclonal antibodies) and MuSK agonists represent promising future therapeutic strategies for MuSK-MG. Overall, this review provides a definitive summary of the present practices and future strategies for the diagnosis and treatment of MuSK-MG, laying out clear markers for further studies that have to be undertaken to enhance our understanding of this condition.
如何引用
AMA
Xinyue Zhou, Jing Zhang, Haiyan Dong, Xinxin Cui, Hanxin Zhang, Mengdi Zhang, et al. MuSK myasthenia gravis: from antigen-antibody to clinical translation.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1732705.
APA
Xinyue Zhou, Jing Zhang, Haiyan Dong, Xinxin Cui, Hanxin Zhang, Mengdi Zhang, et al (2026). MuSK myasthenia gravis: from antigen-antibody to clinical translation.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1732705
GB/T 7714
Xinyue Zhou, Jing Zhang, Haiyan Dong, Xinxin Cui, Hanxin Zhang, Mengdi Zhang, et al. MuSK myasthenia gravis: from antigen-antibody to clinical translation.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1732705.
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