Neurology：重症肌无力患者血清抗体类型决定预后

如果重症肌无力(MG)患者血清肌肉特异性激酶(MuSK)抗体阳性则其症状可能更为严重，达到缓解的目标可能更难。

“临床医师在诊断与治疗重症肌无力时应该充分考虑到这些特点，”Carlo Antozzi(意大利米兰的"Carlo Besta"神经研究所基金会)和她的同事们说。大约85%的MG患者(AChR-阳性患者)中检测出MG免疫标志物抗乙酰胆碱受体(AChR)抗体(AChR-阳性患者)。余下的AChR-阴性患者可能有MuSK抗体(MuSK-阳性患者)，而其他患者没有这两种抗体，即为双重阴性(DN)患者。

在1980年1月至2009年12月期间的一项677名患者的回顾性研究发现，MuSK-阳性患者(n = 55)比AChR-阳性患者(n=517)和DN病人(n=105)的发病时的临床分期及临床最严重程度都更为严重。临床分期是通过以下类别进行分级的：眼肌型MG；全身型MG(包括四肢和躯干肌肉)，延髓型MG(延髓肌肉受累的MG)，呼吸系统受累的MG(呼吸系统受累的全身或延髓型MG)；药物缓解，完全稳定的缓解型(CSR，停止治疗至少1年没有症状或MG标志)；MG导致死亡。如神经病学报道，60.1%的MuSK-阳性患者在发病时出现延髓型MG，相比之下AChR-阳性患者为35.2%而DN患者为23.8%。此外， MuSK-阳性患者中仅有3.6%达到CSR，相比之下，AChR-阳性患者为22.2%，DN患者为21.9%。

多变量分析显示，在整个群体中，发生于40岁前且临床分期为眼肌型或全身型患者达到CSR的可能性与抗体类型具有显着关联，危险比分别为为1.96、8.05和3.71。“MuSK抗体阳性的患者群临床差异与较低的CSR发生率相关，”Antozzi和他的同事们说。“事实上，MuSK抗体属于IgG4亚型的一种，不与补体结合，能造成神经肌肉接合点的中断，从而产生信号传输障碍，对参与突触后膜AChR固定与稳定的几个蛋白质产生复杂影响，”他们解释到。研究认为，MuSK-阳性患者达到CSR的低百分比暗示从发病开始就需要更积极的治疗，并且类固醇和免疫抑制等药物的使用应尽早的考虑在治疗方案之内。
与肌无力相关的拓展阅读：

• AAN 2013：重症肌无力治疗新药研究
• 进行性肌无力伴肌萎缩 更多信息请点击：有关肌无力更多资讯

Complete stable remission and autoantibody specificity in myasthenia gravis.
OBJECTIVES
Patients with myasthenia gravis (MG) are subgrouped as acetylcholine receptor (AChR)-positive, muscle-specific kinase (MuSK)-positive, and AChR/MuSK-negative MG (or double negative [DN]) on the basis of autoantibody assay. We investigated the relationships between autoantibody specificity, main clinical features, and outcome of the disease, in particular the occurrence of complete stable remission (CSR), by means of a retrospective study on a cohort of 677 Italian patients with MG.
METHODS
A total of 517 (76%) patients with AChR-positive MG, 55 (8%) patients with MuSK-positive MG, and 105 (16%) patients with DN MG were included in the study. Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate associations between baseline characteristics, antibody specificity, and CSR.
RESULTS
Clinical stage at onset and at maximal worsening was more severe for MuSK-positive patients: bulbar impairment at maximal worsening was found in 83.6% of MuSK-positive patients compared with 58.6% of AChR-positive patients and 43.8% of DN patients (p < 0.001). Baseline characteristics of AChR-positive and DN patients were similar. CSR was observed in 3.6% of MuSK-positive patients compared with 22.2% of AChR-positive and 21.9% of DN patients. In the whole MG cohort, onset before age 40 (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.27-3.02, p = 0.002) and ocular and generalized clinical stages at maximal worsening were associated with CSR (ocular, HR = 8.05, 95% CI 1.88-34.53, p = 0.005; generalized, HR = 3.71, 95% CI 1.16-11.90, p = 0.023; bulbar, HR = 3.16, 95% CI 1.00-10.05, p = 0.051).
CONCLUSIONS
MuSK antibodies identify a clinically distinguishable, more severe form of MG since the disease onset, with a lower occurrence of CSR. These features should be considered by the clinician in the management of this particular form of MG.