重症肌无力乙酰胆碱受体抗体对大鼠神经元烟碱型乙酰胆碱受体作用

为了阐明重症肌无力（ＭＧ）患者中枢神经系统（ＣＮＳ）受损机制，本研究利用免疫组化和脑干听觉诱发电位仪观察了从ＭＧ患者血中提取的乙酰１胆碱受体抗体（ＡＣｈＲａｂ）与神经元烟碱型乙酰胆碱受体（神经－ｎＡＣｈＲ）之间的免疫结合反应及其对大鼠脑干听觉传递中枢功能的影响。结果：首次表明神经－ｎＡＣｈＲ样阳性免疫结合反应弥散地分布于大鼠ＣＮＳ许多部位，如大鼠大脑皮层、脑干各颅神经运动核团、听神经核、脊髓前角运动元和小脑皮层等。注入脑室系统的ＡＣｈＲａｂ除了引起大鼠脑干听觉传递中枢功能障碍外，还引起ＭＧ动物模型样症状。提示：ＡＣｈＲａｂ可与ＣＮＳ中的神经－ｎＡＣｈＲ免疫交叉结合；ＡＣｈＲａｂ的病理作用不仅仅局限于神经肌接头处肌－ｎＡＣｈＲ，还可波及到ＣＮＳ中的神经－ｎＡＣｈＲ。     

抗乙酰胆碱酯酶抗体阳性的重症肌无力4例报告

抗乙酰胆碱酯酶抗体阳性的重症肌无力４例报告北京医科大学第一医院神经内科（１０００３４）唐健袁锦楣郝洪军重症肌无力（ＭＧ）是神经系统较常见的疾病，一般认为与自身免疫有关。目前在ＭＧ中发现２种抗突触结构的自身抗体。一种为抗乙酰胆碱受体的抗体，另一种为抗突...     

抗乙酰胆碱受体抗体检测的意义及局限性

乙酰胆碱受体 (ａｃｅｔｙｌｃｈｏｌｉｎｅｒｅｃｅｐｔｏｒ,ＡＣｈＲ)是神经肌肉接头 (ＮＭＪ)处的神经递质 ,重症肌无力 (ｍｙａｓｔｈｅｎｉａｇｒａｖｉｓ ,ＭＧ)作为神经肌肉接头处的自身免疫病 ,已被临床研究及其实验动物模型所证实[1] ,而且 ,已经证实ＭＧ是乙酰胆碱受体抗体 (ＡＣｈＲ -Ａｂ)介导的自身免疫病 ,因此该抗体的检测也已成为ＭＧ临床诊断的重要手段。Ｐａｔｒｉｃｋ和Ｌｉｎｄｓｔｒｏｍ(1973)用电鳗电器官提取纯化的ＡＣｈＲ作为抗原 ,与福氏完全佐剂混合后免疫家兔 ,在第 2次注射抗原后 ,成功地制成了实验性自身免疫…     

磺脲类药物继发失效与成人晚发型自身免疫性糖尿病

目前已了解Ⅰ型糖尿病（ＤＭ）是一种针对胰岛β细胞的自身免疫性疾病,伴有胰小岛淋巴细胞浸润、循环中出现特异性的自身抗体,如胰岛细胞抗体（ＩＣＡ）、谷氨酸脱羧酶抗体（ＧＡＤＡｂ）等［１］。而Ⅱ型ＤＭ则是在胰岛素（Ｉｎｓ）抵抗伴Ｉｎｓ分泌相对或绝对不足基础上发生的［２］。但近年来研究发现,一些成年发病、起病时表现类似Ⅱ型ＤＭ的病人也有上述自身抗体,提示病人体内有慢性自身免疫性胰小岛炎。由此提出“成人晚发型自身免疫性糖尿病（ＬＡＤＡ）”的概念［３］。本研究通过测定磺脲类药物（ＳＵ）继发失效的成年ＤＭ患…     

心肌炎和扩张型心肌病抗心肌自身抗体的研究进展

心肌炎（ＭＣ）和扩张型心肌病（ＤＣＭ）的发病与病毒感染后的自身免疫有关,两种疾病可能是心肌器官特异性自身免疫性疾病的不同阶段,ＤＣＭ在很多情况下被认为继发于ＭＣ。目前已有大量报道在ＭＣ和ＤＣＭ患者血清标本中检测出抗心肌的自身抗体（如抗线粒体ＡＮＴ抗体,抗β－肾上腺素能受体抗体,抗胆碱能受体抗体,抗肌球蛋白抗体,抗热休克蛋白抗体,抗支链α酮酸脱氢酶复合体抗体等）,这些自身抗体在ＭＣ和ＤＣＭ发病中起重要作用,本文就这方面的进展作一简要综述。     

糖尿病患者谷氨酸脱羧酶自身抗体测定的临床意义

应用间接ＥＬＩＳＡ法测定３７例胰岛素依赖型糖尿病（ＩＤＤＭ）患者血清谷氨酸脱羧酶（ＧＡＤ）自身抗体，并以非胰岛素依赖型糖尿病（ＮＩＤＤＭ）、及其它自身免疫性疾病、正常人各３０例作对照，同时用间接免疫荧光法测定胰岛细胞浆抗体（ＩＣＡ）作比较。结果：ＩＤＤＭ患者的阳性率高达８３．８％（３１／３７），ＮＩＤＤＭ患者为１６．７％（５／３０），而其它自身免疫性疾病及正常人无１例阳性。在ＩＤＤＭ患者中，ＧＡＤ     

重症肌无力合并癫痫10例临床特点分析

重症肌无力（ＭＧ）传统上认为是骨骼肌受累,近年来有学者发现ＭＧ可有骨骼肌以外受影响的情况,如锥体束征、记忆认识功能损害［１］等。现将我们观察的１９９６～１９９９年２８０例ＭＧ患者中１０例合并癫痫发作的特点分析如下。１材料和方法１．１一般资料１０例ＭＧ合并癫痫病人,男２例,女８例,起病年龄７～４８岁,平均（３０± １２）岁,患病时间３个月至５年,平均（１０±８）个月。按Ｏｓｓｅｒｍａｎ分型,Ⅱａ型 １例,Ⅱｂ型 ３例,Ⅲ型４例,Ⅳ型２例。此１０例病人既往无癫痫史。１．２肌无力评分　针对ＭＧ合并癫痫相…     

慢性丙型病毒性肝炎患者的自身抗体检测

分别用免疫印迹法、免疫胶乳法、放射免疫法测定了５６例慢性丙型肝炎患者的７种ＥＮＡ多肽抗体、类风湿因子及二种甲状腺抗体（ＴＭ、ＴＧ）。发现慢性丙肝患者血清中有多种自身抗体，其中以抗－ｕ１ＲＮＰ、抗－ＳＳ－Ａ二种ＥＮＡ多肽抗体、ＲＦ的检出率最高。７５％（４２例）丙肝患者血清中可检测到一种以上的自身抗体。在丙肝病毒复制指标ＨＣＶ－ＲＮＡ阴转后，自身抗体检出率明显下降，说明在慢性丙型肝炎存在与ＨＣＶ复制有关的自身免疫现象，这有助于进一步揭示其发病机理。     

I型糖尿病患者谷氨酸脱羧酶反应性T淋巴细胞与自身抗体的比较

应用ＮＡＧ微量酶反应比色法反映细胞增殖，检测３０例Ｉ型糖尿病（Ｉ型ＤＭ）患者外周血单个核细胞对谷氨酸脱羧酶（ＧＡＤ）的反应性，并以Ⅱ型糖尿病（Ⅱ型ＤＭ）、其它自身免疫性疾病、正常人各３０例作对照。同时应用间接ＥＬＩＳＡ法检测Ｉ型ＤＭ患者血清中ＧＡＤ自身抗体作比较。结果ＧＡＤ反应性Ｔ淋巴细胞Ｉ型ＤＭ的阳性率为３６．７％（１１／３０），其它自身免疫性疾病１０％（３／３０），而Ⅱ型ＤＭ和正常对照组无一例     

神经系统疾病

神经系统疾病２１１重症肌无力患者周围血淋巴细胞亚群频率的变化与免疫抑制剂有关［英］／ＣｒｏｓｔｉＦ…∥Ｊ　Ｎｅｕｒｏｌ．－１９９４，２４１．－２１８～２２２本文检测了６７例重症肌无力（ＭＧ）患者与５０例健康对照组的周围血淋巴细胞（ＰＢＬｓ）亚群表型，...     

Myasthenia gravis and hyperthyroidism: two cases

It is well known that hyperthyroidism occurs in approximately 2 to 17.5% of patients with myasthenia gravis. Hyperthyroidism may influence the clinical course of myasthenia gravis. We report the cases of two patients, a 53-year-old man and an 18-year-old woman, who had both severe myasthenia gravis and hyperthyroidism due to Graves' disease. Myasthenia gravis affected in particular facio-ocular areas with diffuse myopathy and signs of neuromuscular block on the electromyogram. In one patient, the diagnosis of thyroid disease was made three months before the diagnosis of myasthenia gravis while in the other, thyroid disease was recognized four months after myasthenia gravis. Myasthenia gravis worsened after the development of hyperthyroidism in the second patient. Both patients were given anti-cholinesterase drugs. One underwent thymectomy. Radioiodine used for the treatment of hyperthyroidism improved the symptoms of myasthenia gravis in the first patient. The association of myasthenia gravis and hyperthyroidism is more than a coincidence; our cases illustrate the difficult diagnosis and management of these diseases. Clinicians should look for myasthenia gravis in hyperthyroid patients and vice versa, especially when symptoms of myasthenia gravis or hyperthyroidism worsen.     

Coexistence of systemic lupus erythematosus and myasthenia gravis: two distinct populations of anti-DNA and anti-acetylcholine receptor antibodies

A woman with a four-year history of systemic lupus erythematosus (SLE) developed myasthenia gravis (MG). The clinical features of lupus disappeared slowly while the myasthenic syndrome became predominant. However, her serum was positive for anti-DNA and anti-acetylcholine receptor antibodies. Cross-reactivity between anti-DNA antibodies and anti-acetylcholine receptor antibodies was not demonstrated, suggesting the presence of two different populations. A cellular immunology profile was normal as expected in MG and in contrast to SLE. Conceivably, SLE and MG might represent two opposite extremes in the spectrum of autoimmune diseases.     

High prevalence of systemic lupus erythematosus in 78 myasthenia gravis patients: a clinical and serologic study

OBJECTIVE: The objective of this study was to define the prevalence of systemic lupus erythematosus (SLE) in patients with myasthenia gravis (MG). METHODS: Seventy-eight MG patients recruited unselectively from Israeli MG database were evaluated by medical history, physical examination and serology (ANA at 1:100 and anti-ds-DNA at 1:10 dilution) for the presence of SLE, which was defined by the presence of four or more American College of Rheumatology diagnostic criteria. RESULTS: Thirty-one (40%) of our patients were males and 47 (60%) were females. Their mean age at time of the study was 51.5 +/- 14.5 years. Forty patients (51%) had an early-onset disease (<40 years); 90% had generalized and 10% had limited ophthalmic MG. Significant titers of ANA and ds-DNA autoantibodies were observed in 38.5% and 19.2% of the patients. In six (7.7%), a definitive diagnosis of SLE was established (MG was first diagnosed; there was no association with previous thymectomy), three of them revealed lupus-related neurologic manifestations. All six patients were females with an early onset generalized MG. CONCLUSION: High prevalence of SLE and lupus-related autoantibodies exist in female MG patients. Thus, MG patients should be evaluated for the coexistence of SLE, and assessment for MG is suggested in lupus patients with unexplained muscular weakness.     

Seronegative myasthenia gravis and Graves' disease. Is there a link?

Graves' disease (GD) and myasthenia gravis (MG) are common autoimmune diseases but their coexistence is very rare. They may possibly share the same pathogenetic mechanisms. Recent research has shown the involvement of autoantibodies, lymphocytes, cytokines and chemokines in the pathogenesis of MG and GD. It appears that Th17 cell lineage is involved in autoimmune thyroid disease (AITD) and seems to be key factor in the development of both MG and GD.A 34-year-old male with seronegative myasthenia gravis due to thymic hyperplasia was diagnosed with also GD and opthalmopathy. Several diagnostic and therapeutic issues regarding the relevant literature are discussed.     

Increased frequency of euthyroid ophthalmopathy in patients with Graves' disease associated with myasthenia gravis.

We previously showed that myasthenia gravis (MG) has a mild clinical expression when associated with autoimmune thyroid diseases (AITD). In the present study we have investigated the frequency of thyroid-associated ophthalmopathy (TAO) in patients with Graves' disease (GD) associated with MG as compared with GD patients without MG. A total of 418 patients with GD were studied, 31 with MG and 387 without MG. TAO was evaluated by physical examination, exophthalmometry, computerized tomography, and computerized visual fields assessment. The overall prevalence of TAO was similar in GD patients with MG (61.2%) and in those without MG (56.4%). When the analysis was restricted to GD patients with ocular MG, a greater frequency of TAO was found (84.6%), compared with GD patients without MG or with GD patients with generalized MG, although the differences did not reach the statistical significance. GD patients with MG had a significantly greater prevalence (12.9%) of euthyroid ophthalmopathy (clinically overt ophthalmopathy without previous and/or current hyperthyroidism) than those without MG (3.1%; p = 0.003). The results suggest a preferential association between the ocular manifestations of GD and MG, which may be due to immunological cross-reactivity against common autoimmune targets in the eye muscle as well as to a common genetic background.     

The co-existence of myasthenia gravis in patients with myositis: A case series

ObjectiveMyositis and myasthenia gravis (MG) are both autoimmune disorders presenting with muscle weakness. Rarely, they occur simultaneously in the same patient. Since the management of myasthenia gravis differs from that of myositis, it is important to recognize when patients have both diseases. We reviewed the cases of 6 patients with both myositis and MG to identify clinical features that suggest the possibility of co-existing MG in myositis patients.MethodsWe identified 6 patients with dermatomyositis or polymyositis and MG. We reviewed their medical records to assess their clinical presentations, laboratory findings, and electrophysiological features.ResultsAll 6 patients had definite dermatomyositis or polymyositis by the criteria of Bohan and Peter as well as electrophysiologic and/or serologic confirmation of MG. Among overlap patients, 5/6 (83%) had bulbar weakness, 2/6 (33%) had ptosis, and 1/6 (17%) had diplopia. Fatigable weakness was noted by 5/6 (83%) patients. Treatment with pyridostigmine improved symptoms in 5/6 (83%) patients. High-dose steroids were associated with worsening weakness in 2/6 (33%) patients.ConclusionsProminent bulbar symptoms, ptosis, diplopia, and fatigable weakness should suggest the possibility of MG in patients with myositis. A suspicion of MG may be confirmed through appropriate electrophysiologic and laboratory testing. In those with myositis–MG overlap, high-dose steroids may exacerbate symptoms and pyridostigmine may play an important therapeutic role.     

Myasthenia gravis and hepatitis C virus infection

SUMMARY. Chronic hepatitis C virus (HCV) infections are often associated with extrahepatic immunological manifestations, including various autoimmune disorders. The aims of this study were to determine the prevalence of HCV markers in patients with myasthenia gravis (MG) and to determine any relationship with HCV infection. Eighty-three patients with MG, 40 men aged 20–93 years and 43 women aged 13–87 years (mean age 54 years) were studied. The MG patients were positive for antibody to acetylcholine receptor, in addition, their sera was analysed for antibody to HCV (HCVAb) and HCV RNA. HCVAb was detected in two of the 83 patients (2.4%). Four patients were repeatedly HCV RNA positive. They were infected by HCV genotype 1 (one patient), HCV genotype 2a (two patients) and an undetermined HCV genotype in one patient. They received plasmapheresis or intravenous immunoglobulin treatment. Among the four patients, one was infected after the onset of MG without receiving a blood transfusion or using intravenous drugs. The other three had chronic hepatitis C which was discovered at the same time as MG and only one patient had been exposed to blood products. The prevalence of HCV markers in patients with MG (4.8%) was higher than that reported for the general French population, about 1%. This prevalence is similar to that occurring in patients exposed to plasmapheresis or intravenous immunoglobulin. In conclusion, HCV appears to play little, if any, role in causing MG. The higher prevalence of infection among MG patients may be related to transmission in the course of therapy.     

D-penicillamine induced myasthenia gravis in a patient with rheumatoid arthritis

We have encountered a 53 year-old female with myasthenia gravis (MG) possibly induced by the treatment with D-penicillamine (D-pc). She has had a long-standing history of rheumatoid arthritis (RA) prior to the onset of MG. The diagnosis for MG was made based on the clinical findings and tests including antiacetylcholine receptor antibody and EMG. Although the drug had been efficacious for RA, it was discontinued after the development of MG. The symptoms and signs for MG were immediately disappeared, whereas clinical manifestations for RA was relapsed shortly after. Since D-Pc has been frequently used for the treatment of RA, an awareness of this side effect appears to be of particular importance for physicians in clinical practice who deal with RA. Furthermore, it may also provide some important immunological insights into the study of pathogenesis of MG.     

Isoniazid-triggered pure red cell aplasia in systemic lupus erythematosus complicated with myasthenia gravis

A 47-year-old woman who had been treated for systemic lupus erythematosus (SLE) with myasthenia gravis (MG) was admitted to our hospital with acute onset of severe anemia after administration of isoniazid. Pure red cell aplasia (PRCA) was confirmed by elevated serum iron levels, reticulocytopenia and bone marrow aspiration showing a remarkable reduction of erythroblasts. Finally, cyclosporine A successfully improved PRCA. Although both SLE and MG have the potential complication of PRCA, we report here a case of isoniazid-triggered PRCA.     

The toxicity of D-penicillamine in systemic sclerosis

We studied D-penicillamine toxicity in 259 patients with systemic sclerosis treated since 1972. The average daily dose of 635 mg was given for a mean of 1.8 years. Of patients with systemic sclerosis, 47% has side effects from D-penicillamine treatment, similar to the 56% of 807 patients with rheumatoid arthritis in seven separate series. Individual manifestations of toxicity included rash, proteinuria, gastrointestinal symptoms, dysgeusia, oral ulcers, thrombocytopenia, and neutropenia. Four episodes each of myasthenia gravis and pemphigus occurred in our patients; both were reported rarely in patients with rheumatoid arthritis. Adverse effects occurred more frequently after rapid increases in dosage. Treatment had to be discontinued due to toxicity in 29% of patients with systemic sclerosis and in 33% of those with rheumatoid arthritis. Although toxic, with a high frequency of adverse effects, D-penicillamine can be used safely in the treatment of systemic sclerosis. Pemphigus and myasthenia gravis may occur more frequently with therapy for systemic sclerosis than with that for rheumatoid arthritis.