Pathomechanism of myathenia gravis with anti-MuSK antibodies and without anti-acethylcholine receptor antibodies

重症肌无力（MG）是一种抗体介导的神经肌肉交界处自身免疫性疾病。在大约80%的患者中，自身抗体被归类为血清阴性。2001年，Hoch等人首次发现，70%的achr - ab血清阴性的MG患者，而不是achr - ab血清阳性的MG患者，具有针对肌肉特异性酪氨酸激酶（MuSK）的血清自身抗体，这种抗体在突触形成过程中介导agrin诱导的achr聚集，也在成熟的神经肌肉连接处表达。随后对achr - ab血清阴性MG患者的研究报告血清阳性率从3.8%到71%不等，achr - ab血清阴性MG患者有110kDa蛋白的抗体，鉴定为MuSK。MuSK ab阳性MG的临床表现如下：1)女性为主，发病年龄在20 ~ 60岁之间；2)患者有明显的颈部或呼吸肌无力；3)胆碱酯酶抑制剂的反应不同；4)所有眼部型MG患者MuSK抗体均为阴性；5)无胸腺瘤，胸腺切除术后无改善。6)大多数患者对血浆置换和类固醇治疗反应良好，但有一部分MuSK Ab阳性MG患者出现肌肉萎缩，预后较差。麝香Ab阳性MG对运动终板的病理观察结果如下：所有MuSK Ab阳性MG患者均表现为ii型纤维萎缩，但未见肌病改变。突触后区域变小并保持突触后密度。MuSK抗体状态应有助于诊断不典型表现的MG，并确保适当的患者治疗。需要进一步的研究来阐明MuSK抗体的发病机制。

Myasthenia gravis(MG) is an antibody-mediated autoimmune disease of the neuromuscular junction. In approximately 80% of patients, auto-antibodies are classified as seronegative. In 2001, Hoch et al, first showed that 70% of AChR-Ab-seronegative MG patients, but not AChR-Ab-seropositive MG patients, have serum auto-antibodies against the muscle-specific tyrosin kinase(MuSK), which mediates agrin-induced clustering of AchRs during synaps formation, and is also expressed at the mature neuromuscular junction. Subsequent studies of AChR-Ab-seronegative MG patients reported seropositivity from 3.8% to 71% and that AChR-Ab-seronegative MG patients had antibodies to a 110kDa protein, identified as MuSK. Clinical aspects of the MuSK Ab-positive MG are the following ; 1)female-dominant, with onset between ages 20 to 60 years, 2)patients had prominent neck or respiratoru muscle weakness, 3)response to cholinesterase inhibitors was variable, 4)all patients with ocular type MG are negative for MuSK antibodies, 5)absence of thymoma, and no improvement after thymectomy. 6)most patients had a good response to plasma exchange and steroid therapy, but a proportion of MuSK Ab positive MG patients who present muscle atrophy had a poor prognosis. Pathological study of motor end-plate from the MuSK Ab- positive MG show the following results ; all of the MuSK Ab- positive MG patient showed typeII fiber atrophy but there are no myopathic changes. The postsynaptic area become small and preserved of postsynaptic density. MuSK antibody status should help diagnose MG with atypical presentations and ensure appropriate patient treatment. Furtherexaminations to elucidate the pathomechanism of MuSK antibodies are needed.