Serum complement composition of myasthenia gravis

Serum complements of C1q C1, C4, BF, C1-INH and C5 were measured by single immunodiffusion in 54 patients with myasthenia gravis (MG), 46 normal control (NC) and 42 cases of other neurological disorders. It was found that C1-INH, C5 levels in MG were significantly higher than that in other groups (P less than 0.01). The serum levels of C1-INH, C5 were not related to the clinical type and the stage of the illness. These data suggest that endplate receptors might be disrupted through complement mediated immunoreaction.     

The role of antibodies in myasthenia gravis

Myasthenia gravis is an autoimmune disease associated with antibodies directed to the postsynaptic acetylcholine receptor. These antibodies reduce the number of receptors. Autoantibodies against AChR and other muscle antigens can be used for the diagnosis of myasthenia gravis and related disorders. The origin and the role of these antibodies in the disease are discussed. Experimental autoimmune myasthenia gravis, an experimental model closely mimicking the disease, has provided answers to many questions about the role of antibodies, complement macrophages and AChR anchor proteins. Genetically modified anti-AChR antibodies may also be used in the future to treat myasthenia.     

Soluble terminal complement components in human myasthenia gravis

The loss of membrane acetylcholine receptor (AChR) leading to muscle weakness and impaired neuromuscular junction (NMJ) transmission in human myasthenia gravis (MG) is in part due to complement mediated muscle membrane damage. This has been supported by the histologic finding of C9 at the NMJ in human MG. We evaluated for evidence of terminal complement components in plasma by using an ELISA for SC5b-9 in 42 separate plasma samples from 31 patients with MG and from healthy controls. Abnormal elevations of SC5b-9 was found in 18 of 31 patients (58%) at one or more time points when plotted on a standard positive dilution curve. Multiple samples were available from 8 patients over time. Clinical deterioration in some, but not all, was accompanied by an increase in SC5b-9 values. There was no clear distinction in the group as a whole between MG severity or AChR antibody levels and SC5b-9 values. This supports the potential role of complement-mediated muscle membrane damage in the pathogenesis of human MG, but also demonstrates that plasma levels as measured by ELISA do not always correlate with disease activity.     

Clinical pitfalls and serological diagnostics of MuSK myasthenia gravis

Journal of Neurology - We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of...     

HLA,anti-DNA,and complement in myasthenia gravis

Twenty-seven patients (18 females and 9 males) with myasthenia gravis were HLA-A, -B, -C, and -D typed, and the results were analyzed with relation to evidence of immunodeficiency, thymic disease, and associated autoimmune processes. An association of A1, B8, and DRW3 appeared to identify a group of 8 females with higher mean anti-DNA, lower mean C4, and lower mean E. coli antibody titer than other females in whom CW4 (with or without BW35) was common (6 of the remaining 10 females were in this category). Antiacetylcholine receptor (anti-AChR) autoantibody and reduced serum lgM and isohemagglutinin titers were not clearly related to particular HLA specificities. These results suggest that HLA-A1, -B8, -DRW3, and -CW4 may be related to associated phenomena rather than playing a major role in the development of anti-AChR and myasthenia gravis.     

Thymectomy: role in the treatment of myasthenia gravis

Thymectomy is a frequently used treatment for myasthenia gravis (MG) and is virtually always indicated in MG patients who have a thymoma. However, the evidence for thymectomy in non-thymomatous MG remains less certain—no randomised controlled trials have been published to date, although one is currently underway. We reviewed the management and clinical outcome of patients with MG who underwent thymectomy over a 12 year period. Eighty-nine patients who underwent transsternal thymectomy were identified. A thymoma was identified on histology in 24 %, whereas 48, 9 and 19 % had hyperplastic, atrophic and normal thymic histology, respectively. One patient developed post operative myasthenic crisis but generally the procedure was well tolerated. Outcome was favourable for the majority of patients, with 34 % achieving complete stable remission (CSR) and an additional 33 % achieving pharmacological remission. Moreover, steroid requirements fell progressively during follow-up. Patients with a hyperplastic gland had a significantly greater chance of achieving CSR compared to other histological subtypes and the incidence of CSR increased with a longer duration of follow-up. Thymectomy for MG is generally safe and well tolerated and is associated with a sustained improvement of symptoms in the majority of patients.     

Plasma exchange in myasthenia gravis: changes in serum complement and immunoglobulins

Serum concentrations of C4, IgG, IgA, and IgM were followed in 8 selected patients with myasthenia gravis (MG) during a 5-day course of plasma exchange (PE), using donor plasma as a replacement solution. C3 activation products (C3b, iC3b and C3c) and the terminal SC5b-9 complement complex were measured in 4 of the patients. All patients improved during the treatment, including 2 patients without detectable antibodies to AChR in serum. The main findings of the study were marked complement activation and an approximately 50% fall in the serum concentrations of IgM and C4 during PE, independent of the concentrations in the donor plasma. The concentrations of IgG and IgA did not change significantly. The fall in C4 during PE is presumably caused by C4 consumption. We postulate that the fall in IgM is an effect of a complement-induced vasodilatation and that PE-induced complement consumption may influence the effect of PE in patients with MG.     

Thymectomy: its role in the management of myasthenia gravis

The management and clinical course of patients with myasthenia gravis admitted to a neurological intensive therapy unit (ITU) for thymectomy over a 66 month period were reviewed. There were 53 patients, 20 male and 33 female, mean age 35.2 years (18–74) and median ITU stay of 5 days (2–30). Indications for thymectomy were thymic enlargement on computed tomography (34%), persistence of generalized symptoms (38%), a combination of both (20%), steroid side effects or dependency (4%) and progressive bulbar symptoms (4%). Following thymectomy, thymic histology revealed thymic follicular hyperplasia (26/53; 49%), atrophy (11/53; 21%), thymoma (12/53; 23%) and normal thymus (4/53; 8%). Post-operatively 23% required prolonged intubation (> 48 hrs); two patients required a tracheostomy 10 and 13 days post-operatively. Plasma exchange was required for two patients (3.8%) due to persistent severe myasthenic weakness. Three patients (6%) developed a post-operative chest infection and one pseudomembranous colitis. There were no post-operative mortalities during the study period. After 2 years, 35% of patients were in remission and 46% had ocular or mild generalized symptoms only. Thymectomy for myasthenia gravis is followed by sustained clinical improvement in the majority of patients. The appropriate post-operative management of these patients is best undertaken in a specialized neuro-intensive care setting.     

Clinical and serological study of myasthenia gravis in HuBei Province, China

Background

Ocular and childhood myasthenia gravis (MG) cases seem relatively more common in Oriental than in Caucasian populations, but there have been no comprehensive serological studies on patients from mainland China.

Methods

391 unselected patients with MG attending Tongji Hospital in WuHan (the largest hospital in the province of HuBei, China) were studied during a 15‐month period; most had already received treatment for their condition.

Results

The male to female ratio was 0.8. 50% of the patients were children (<15 years), and age at onset showed a single peak at between 5 and 10 years of age. 64% of the children and 66% of the adults were positive for acetylcholine receptor (AChR) antibodies but the antibody titres were lower than in similar Caucasian studies, although this was partly due to the high incidence of ocular MG. Of the 43 patients with generalised MG without AChR antibodies, only 1 had muscle‐specific kinase antibodies (2.5%) and 2 had voltage‐gated calcium channel antibodies indicating probable Lambert–Eaton myasthenic syndrome. 75% of the children, compared with only 28% of the adults, had ocular MG. Thymoma was evident by MRI in 1.5% of children and in 20% of adults. Despite most patients having received prednisone, very few had obtained full clinical remission.

Conclusion

This study emphasises the frequency of early childhood onset with ocular symptoms and shows that many of these patients have AChR antibodies. By contrast, patients presenting in later age seem to be very uncommon in comparison with recent studies in Caucasian populations.Myasthenia gravis (MG) is the most common primary disorder of neuromuscular transmission. Acetylcholine receptor (AChR) antibodies are present in sera from 80% to 90% of patients with generalised MG, about 50% from those with pure ocular MG and infrequently in healthy people.¹ The remaining 10–20% of generalised patients with MG are AChR antibody negative (seronegative MG, SNMG). IgG autoantibodies to the muscle‐specific kinase (MuSK) were first identified in 70% of patients with generalised SNMG.² However, subsequent reports have found a variable prevalence in different countries, with a low proportion of MuSK antibody‐positive MG in one study from Taiwan³ (reviewed in Vincent and Liete⁴).A number of studies indicate that MG in Oriental populations may be clinically different from that in Caucasians.^5,6,7,8 In particular, paediatric cases are frequent in China, Taiwan and Japan and purely ocular MG is relatively common in children. Since there are also differences in human leucocyte antigen associations between Japanese, Chinese and Caucasian populations,^9,10,11,12 these observations may provide clues to the immunopathogenesis of MG.However, there have been no comprehensive studies of AChR and MuSK antibodies in patients from mainland China. Here, we studied the histories and serology of 391 Chinese patients attending a major hospital in WuHan, China.     

干扰素-γ在重症肌无力发病机制中的作用

重症肌无力(myasthenia gravis,MG)是由乙酰胆碱受体抗体(acetylcholine receptor antibody,AChRAb)介导、细胞免疫依赖性补体参与的自身免疫性疾病,主要累及神经肌肉接头处突触后膜上的     

Memory dysfunction in myasthenia gravis: evidence for central cholinergic effects

Two studies are presented that investigate the possible central cholinergic effects of myasthenia gravis as measured by cognitive dysfunction. In the first study, performance on a battery of cognitive tasks by 12 subjects with myasthenia gravis is compared with that of ten healthy control subjects and ten medical control subjects with chronic disease of a nonneurologic nature. The tests used were the Boston Naming Test, Rey Auditory Verbal Learning Test (AVLT), and the Logical Memory and Design Reproduction portions of the Wechsler Memory Scale (WMS). Results indicate that the myasthenic group was significantly impaired relative to both the medical and healthy control groups for performance on the Boston Naming Test, WMS Logical Memory, and WMS Design Reproduction. Both the myasthenic and the medical control groups were impaired relative to the healthy controls on the AVLT. In the second study, a myasthenic patient had plasmapheresis for treatment of her myasthenia on two separate occasions. Her memory was examined prior to as well as following each series of plasma exchanges with a variation of the Peterson-Peterson consonant trigram task. Results showed that this patient had significantly fewer interference effects and less rapid forgetting following plasmapheresis. The results of these two studies support the hypothesis that myasthenia gravis has central cholinergic effects manifested by cognitive dysfunction.     

Coexistence of myasthenia gravis and serological markers of neurological autoimmunity in neuromyelitis optica

We systematically evaluated the frequency of neurological disorders and muscle and neural autoantibodies in 177 patients with neuromyelitis optica (NMO) and in 250 control subjects (173 healthy; 77 multiple sclerosis, MS, patients). An excess of myasthenia gravis (MG, 2%), and muscle‐type acetylcholine receptor antibody (11%) was detected among NMO patients. The presence of neural or muscle autoantibodies was more common in NMO patients (34%) than in MS patients or healthy controls (7%), P < 0.0001. The coexistence of NMO and MG should be considered in atypical or refractory presentations of either disorder. © 2008 Wiley Periodicals, Inc. Muscle Nerve 39: 87–90, 2009     

Putative role of antireticulin antibody in antiacetylcholine-receptor-antibody-negative myasthenia gravis

It has recently been demonstrated that pathogenic immunoglobulins circulate in the blood of patients with acetylcholine-receptor-antibody (A-AChR)-negative myasthenia gravis (MG). Evidence has been presented that in this form of MG the neuromuscular transmission is impaired by antibodies that bind to endplate determinants other than the AChR. We describe three patients with clinical manifestations of A-AChR-negative MG in whom antibody directed to reticulin (A-Ret) was detected. Antibody directed to reticulin is usually associated with celiac disease; however, none of the patients had symptoms or signs of celiac disease. To our knowledge, the association of A-Ret with A-AChR-negative MG has not been reported before. We postulate that A-Ret might help to differentiate between A-AChR-negative MG and congenital myasthenia. Further studies are needed to determine whether A-Ret plays a pathogenic role in A-AChR-negative MG or should instead be considered as an epiphenomenon.     

CD40配体在重症肌无力发病机制中的作用探讨

目的　研究 CD4 0配体 (CD4 0 L)在重症肌无力 (MG)患者主要致病因素产生中的作用 ,从而探讨CD4 0 L 在 MG发病机制中的作用。方法　 MG急性期组 10例 ,MG非急性期组 15例 ,设健康对照组 16例。分离外周血单个核细胞 (PBMC) ,分组用植物血凝素 (PHA)和美洲商陆原 (PWM)刺激剂刺激进行单个核细胞培养 :(1)PHA组 :即用 PHA刺激。培养后收集上清检测 γ-干扰素 (IFN- γ)和白细胞介素 4 (IL- 4 ) ;(2 ) PWM组 :即用 PWM刺激。培养后收集上清检测抗乙酰胆碱受体抗体 (Ach Rab)和抗突触前膜受体抗体 (Psm Rab)。比较两组中抗CD4 0 L 单克隆抗体 (CD4 0 L m c Ab)干预与否的差异并与健康对照组比较。结果　无论 MG急性期组或 MG非急性期组 ,刺激后 Ach Rab、Psm Rab、IFN- γ和 IL- 4水平均比健康对照组显著增高 (P<0 .0 0 1)。MG急性期组 IFN- γ高于 MG非急性期组 (P<0 .0 5 ) ,MG非急性期组 IL- 4高于 MG急性期组 (P<0 .0 5 ) ,CD4 0 L mc Ab干预后 4种因素均基本降至健康对照组水平 (P>0 .0 5 )。结论　在 MG的发生、发展过程中 Th细胞亚类出现不平衡 ,CD4 0 -CD4 0 L 共刺激因子均起重要作用