CorrespondenceLack of Association of Latent Autoimmune Diabetes in Adults (LADA) with Enterovirus Infection

In myasthenia gravis (MG) and experimental autoimmune MG (EAMG), many pathologically significant autoantibodies are directed at the main immunogenic region (MIR), a conformation-dependent region at the extracellular tip of α1 subunits of muscle nicotinic acetylcholine receptors (AChRs). Human muscle AChR α1 MIR sequences were integrated into Aplysia ACh-binding protein (AChBP). The chimera was potent in inducing both acute and chronic EAMG, though less potent than Torpedo electric organ AChR. Wild-type AChBP also induced EAMG but was less potent, and weakness developed slowly without an acute phase. AChBP is more closely related in sequence to neuronal α7 AChRs that are also homomeric; however, autoimmune responses were induced to muscle AChR, but not to neuronal AChR subtypes. The greater accessibility of muscle AChRs to antibodies, compared to neuronal AChRs, may allow muscle AChRs to induce self-sustaining autoimmune responses. The human α1 subunit MIR is a potent immunogen for producing pathologically significant autoantibodies. Additional epitopes in this region or other parts of the AChR extracellular domain contribute significantly to myasthenogenicity. We show that an AChR-related protein can induce EAMG. Thus, in principle, an AChR-related protein could induce MG. AChBP is a water-soluble protein resembling the extracellular domain of AChRs, yet rats that developed EAMG had autoantibodies to AChR cytoplasmic domains. We propose that an initial autoimmune response, directed at the MIR on the extracellular surface of muscle AChRs, leads to an autoimmune response sustained by muscle AChRs. Autoimmune stimulation sustained by endogenous muscle AChR may be a target for specific immunosuppression.     

Initial Repetitive Nerve Stimulation Test Predicts Conversion of Ocular Myasthenia Gravis to Generalized Myasthenia Gravis

Background and PurposeA major concern with ocular myasthenia gravis (MG) is the potential conversion to generalized MG. This study was conducted to determine if the repetitive nerve stimulation (RNS) test could predict the conversion from ocular to generalized MG.MethodsThe RNS test was conducted in a consistent manner on five muscles in the face and limbs in every patient. Subjects were divided into those who remained as ocular MG (ROMG group) and those who experienced conversion to generalized MG during follow-up (GOMG group).ResultsConversion to generalized MG occurred in 24 (21.4%) of 112 MG patients with ocular onset. The proportion of patients displaying abnormal decreases in responses in the trapezius, abductor digiti minimi, or flexor carpi ulnaris muscles on the RNS test was higher in the GOMG group (p<0.001, p=0.002, and p<0.001, respectively). The Cox proportional-hazards model revealed that an abnormal result on the RNS test was significantly associated with conversion to generalized MG [hazard ratio (HR)=3.13, 95% confidence interval (CI)=1.18–8.32]. Notably, the HR was higher for abnormal results on the RNS test for the limb muscles, at 5.19 (95% CI=2.09–12.90).ConclusionsAn abnormal result on the RNS test, especially in the limb muscles, is an independent predictor of the conversion from ocular to generalized MG. Applying the RNS test to limb muscles could be useful for predicting the conversion to generalized MG in patients with ocular onset.     

微小RNA与重症肌无力研究进展

微小RNA(miRNA)是一类进化上保守的内源性单链非编码小RNA分子,长度约为19 ～24个核苷酸,通过靶基因特异性结合从而导致mRNA降解或翻译抑制,在转录后水平调控基因表达.大量研究表明miRNA与多种人类自身免疫性疾病密切相关.重症肌无力(MG)是神经-肌肉接头处传递功能障碍的自身免疫性疾病.探究miRNA在MG发生发展中的分子机制有助于阐明MG的致病机制,为MG的分子诊断和个性化治疗提供重要依据.本文主要对miRNA与MG相关性的研究进展进行综述.     

胸腔镜胸腺扩大切除治疗重症肌无力简

目的 探究胸腔镜胸腺扩大切除术治疗重症肌无力的方法及疗效.方法 选取我院收治的60例重症肌无力患者,随机分为对照组和实验组,每组各30例患者,对照组采用常规手术进行重症肌无力治疗,实验组采用胸腔镜胸腺扩大切除治疗重症肌无力,治疗结束后对两组患者进行疗效与生活质量满意度调查,通过调查结果分析胸腔镜胸腺扩大切除治疗重症肌无力疗效.结果 两组患者治疗满意度结果差异显著,对照组非常满意3例,一般满意17例,不满意10例,满意度66.67%;实验组患者非常满意25例,一般满意4例,不满意1例,满意度达96.67%.结论 胸腔镜胸腺扩大切除治疗重症肌无力得到患者认可,具有安全可靠、长效等特点,疗效等同于其他传统方法,具有实际推广意义.     

A Decrease in the Percentage of CD3+ Cells Is Correlated With Clinical Improvement During Plasmapheresis in Patients With Myasthenia Gravis

Plasmapheresis not only removes circulating antibodies but also modulates cellular immunity, including lymphocyte subsets. To investigate the effect of double‐filtration plasmapheresis (DFPP) on the ratio of lymphocyte subsets in patients with myasthenia gravis (MG), we examined the percentages of B‐cells, T‐cells, T helper (Th) cells, T suppressor (Ts) cells, natural killer (NK) cells, NKT cells, and Th/Ts ratio before and after a single DFPP session and after a course of DFPP. A total of 26 patients were recruited; their peripheral blood lymphocyte subsets were assayed using flow cytometry. After a single session of DFPP treatment, the percentages of T‐cells (P = 0.0200), Th cells (P = 0.0178), and the Th/Ts ratio (P = 0.0309) decreased significantly, whereas the percentage of NK cells (P = 0.0007) increased significantly. More importantly, after one course of DFPP treatment, the reduced clinical quantitative MG (QMG) score was correlated with the decrease of the percentage of T‐cells (r = 0.5005, P = 0.0092). Fourteen thymectomized MG patients had decreased percentages of T‐cells (P = 0.0304) and Th cells (P = 0.0444), whereas they had increased NK cells (P = 0.0197) after a single DFPP session. Here, transiently decreased percentages of T‐cells after the full DFPP course could enhance the effectiveness of plasmapheresis for MG patients.     

Acute presentation of autoimmune hepatitis in a patient with myasthenia gravis, thymoma, Hashimoto thyroiditis and connective tissue disorder

Myasthenia gravis is an antibody-mediated autoimmune disease at the neuromuscular junctions. It can be associated with many other autoimmune diseases. We report a case of acute presentation of autoimmune hepatitis with myasthenia gravis, thymoma, Hashimoto thyroiditis and connective tissue disorder.     

VATS胸腺扩大切除术治疗重症肌无力临床分析

目的评价电视胸腔镜(video-assistant thorascope,VATS)下胸腺扩大切除术治疗重症肌无力(myasthenia gravis,MG)的手术方法和效果。方法回顾性分析36例MG患者的临床资料,其中合并胸腺增生26例,胸腺瘤10例,均行VATS胸腺瘤、胸腺扩大切除术。根据临床Osserman分型:Ⅰ型3例,Ⅱa型22例,Ⅱb型8例,Ⅲ型3例。结果本组手术全部经胸腔镜完成,无中转开胸者。全组手术时间平均80(50~120)min,术中出血量平均80(10~150)ml,留置胸腔引流管1~3 d,引流量平均150(100~500)ml,6例未留置胸管者术后3 d经CT扫描估计胸液量均<200 ml。住院时间3~6 d,术后未出现进行性血胸,无肺及膈神经损伤,无肌无力危象、胆碱能危象发生,无围手术期死亡病例。术后病理:胸腺增生26例,A型胸腺瘤6例,B1型2例,B3型2例(WHO分型)。所有患者随访3~12个月,完全缓解6例(Ⅰ型2例、Ⅱa型4例),占16.7%;部分缓解28例(Ⅰ型1例、Ⅱa型18例、Ⅱb型7例、Ⅲ型2例),占77.8%;稳定2例(Ⅱb型1例、Ⅲ型1例),占5.6%。结论 MG患者行VATS胸腺瘤、胸腺扩大切除术安全、可行,效果理想。     

机器人胸腺扩大切除术在老年重症肌无力患者中的应用

目的评价达芬奇S（da Vinci S）机器人胸腺扩大切除术在老年重症肌无力患者中的应用价值。方法 2009年5月～2011年12月,使用da Vinci S机器人手术系统完成9例老年重症肌无力胸腺及胸腺瘤切除并进行胸腺周围脂肪组织清扫术。全身麻醉下双腔气管插管,仰卧位,一侧胸部垫高30°,术侧胸壁腋前线第5肋间皮肤切开1.5 cm,置入trocar作为观察孔,左右侧各约10 cm的距离（在腋前线第3肋间和锁骨中线第6肋间）置入左右机械手臂trocar,在腋中线第7肋间置入trocar作为辅助操作孔,连接机械手臂。人工气胸压力6～12 mm Hg。胸腺及周围脂肪组织置入一次性取物袋,经辅助操作孔取出。结果 9例均手术成功,无中转开胸。麻醉时间平均180 min（60～210 min）,机器人手术时间平均60 min（30～110min）,术中出血量平均100 ml（30～200 ml）。无手术输血,住ICU时间平均1 d（1～3 d）。9例随访5～32个月,平均12个月,DeFilippi分级1级2例,2级2例,3例5例,有效率100%。结论选择合适的老年患者,使用da Vinci S机器人手术系统行胸腺扩大切除术安全可行,效果确切。     

Muscle‐specific kinase antibodies: A novel cause of peripheral nerve hyperexcitability?

Introduction: Antibodies that target the postsynaptic neuromuscular junction (NMJ) protein, muscle‐specific kinase (MuSK), have been associated with myasthenia gravis (MG), often with cramps and fasciculations, after administration of acetylcholinesterase inhibitors (AChE‐I). Methods: In this report, 2 patients are described with elevated MuSK antibodies and evidence of peripheral nerve hyperexcitability (PNH) unrelated to AChE‐I medication. Results: Patient 1 presented with facial neuromyotonia and fasciculations, without overt weakness. EMG studies demonstrated myokymic discharges in facial muscles, with bursts of discharges after voluntary activation, and widespread fasciculation potentials in limb muscles. Patient 2 presented with bulbar weakness and fasciculations in the tongue and limbs, initially diagnosed as bulbar‐onset amyotrophic lateral sclerosis. Subsequent investigation identified the presence of MuSK antibodies. Conclusions: We hypothesize that MuSK antibodies may induce these phenotypes through disruptive actions at the NMJ, in particular the binding of acetylcholinesterase (AChE) to MuSK via its collagen Q (ColQ) tail, producing a reduction in synaptic AChE activity. Muscle Nerve 48:819–823, 2013