自身免疫多内分泌腺病综合征Ⅲ型合并重症肌无力一例报道及人类白细胞抗原基因分析

1型糖尿病合并自身免疫性甲状腺疾病是自身免疫多内分泌腺病综合征(APS)Ⅲ型最常见的类型,但重症肌无力合并APS Ⅲ型罕见报道。本研究对1例先后出现眼肌型重症肌无力、1型糖尿病、桥本甲状腺炎的APS Ⅲ型合并重症肌无力的男性患者进行了人类白细胞抗原(HLA)基因分析及文献回顾11例APSⅢ合并重症肌无力,发现HLA-D...     

THE THYMUS: EXPERIMENTAL PHYSIOLOGY,AND PATHOLOGY IN MAN

The thymus is an integral part of the immunological system. It is a site of intense lymphopoiesis, especially in early life. Neonatal thymectomy in mice causes runting and death due to gross immunological deficiencies. These deficiencies are determined by lymphopenia, and by lack of a lymphotrophic hormone secreted by the epithelial cells of the medulla; this hormone confers on lymphocytes the capacity to respond to antigenic stimulation. The thymus may be the main source of lymphoid cells carrying new or primary patterns of immune reactivity; it is thus “first-level” or “central” lymphoid tissue, which seeds cells to “second-level” or “peripheral” lymphoid tissues in the lymph nodes and spleen. Pathological lesions of the thymus in man include aplasia, hyperplasia, dysplasia and neoplasia. Gross aplasia characterizes the immunological deficiency diseases of infancy, including the lymphopenic type of congenital agammaglobulinæmia. Hyperplasia accompanies thyrotoxicosis. Dysplasia refers to the lymph follicle-germinal centre development in myasthenia gravis, probably an autoimmune disease, and to the proliferation in the medulla of spindle-epithelial cells in lupus erythematosus, an autoimmune disease. Neoplasia occurs as benign thymoma, which may be accompanied by extrathymic diseases which are possibly autoimmune in origin; these include myasthenia gravis, red cell aplasia, polymyositis, agammaglobulinæmia and lupus erythematosus. These diseases may in some way be caused by the thymoma; alternatively, the thymoma may represent the result of continuing hyperplasia of the thymus provoked by a primary autoimmune process. The place of thymectomy in the treatment of autoimmune disease is discussed. It is an established procedure in myasthenia gravis, and has been successful in two cases of autoimmune hæmolytic anæmia in infancy. We review our experience with thymectomy for three patients with systemic lupus erythematosus.     

Myasthenia gravis and premature ovarian failure

Myasthenia gravis is believed to be an autoimmune disorder that results from antibodies directed against acetylcholine receptors. Not infrequently, it is associated with other autoimmune diseases, and, recently, several cases have been reported of coexistent premature ovarian failure. A 25-year-old nullgravida woman with myasthenia gravis became amenorrheic and then had ovarian failure with increased gonadotropin and negligible estrogen levels. Other endocrine functions were normal. An in vitro assay demonstrated the presence, in serum, of an inhibitor of binding to the luteinizing hormone (LH) receptor that suggested the possibility of a similar autoimmune process underlying the myasthenia gravis and premature ovarian failure. This could be the first case in which both disorders occurred with evidence for an LH receptor antagonist.     

A patient with thymoma and four different organ-specific autoimmune diseases

This is the first report of a patient with four organ-specific autoimmune diseases; myasthenia gravis, type 1 diabetes mellitus, autoimmune hepatitis and Hashimoto's thyroiditis. The clinical history suggests a relationship with a non-removed thymoma. Not only the thymoma seems to have triggered these four diseases, the dramatic progressive course with an active autoimmune hepatitis and high concentrations of multiple autoantibodies was probably also associated with non-removal of the thymoma. Thymectomy should be performed in myasthenia gravis patients with thymoma and associated autoimmune diseases.     

Coexistence of Myasthenia Gravis and Hashimoto's Thyroiditis in a Chinese Woman

Summary: The coexistence of myasthenia gravis and Hashimoto's thyroiditis has rarely been described. A 64-year-old Chinese woman with myasthenia gravis and Hashimoto's thyroiditis is described. The literature on the occurrence of Hashimoto's thyroiditis and myasthenia gravis is briefly reviewed. The relationship between myasthenia gravis and thyroid dysfunction is outlined. It is suggested that the association of myasthenia gravis with Hashimoto's thyroiditis (a long-known autoimmune disease) provides further support to the hypothesis that myasthenia gravis may be an auto-immune disorder.     

重症肌无力患者胸腺自身免疫相关基因表达的研究

目的探讨MG患者和正常对照者的胸腺组织炎症反应与自身免疫性疾病相关基因的表达情况。方法取MG患者（MG组）和正常对照者（对照组）的胸腺组织标本，提取总RNA，反转录合成cDNA后，体外转录合成生物素标记的cRNA与基因芯片进行杂交，通过化学发光法检测基因表达，比较两组胸腺组织基因表达的差异。结果MG组与对照组比较，有61条基因存在显著性差异，其中表达上调33条，下调28条，这些基因包括炎症相关趋化因子基因、细胞因子及其受体基因、与细胞因子产生与代谢有关的基因、细胞因子及其受体相互作用相关的基因、炎症反应相关基因以及体液免疫相关基因等。结论芯片筛选MG患者胸腺自身免疫相关基因表达与正常对照组存在显著差异。     

In vivo therapy with monoclonal anti-I-A antibody suppresses immune responses to acetylcholine receptor

A monoclonal antibody to I-A gene products of the immune response gene complex attenuates both humoral and cellular responses to acetylcholine receptor and appears to suppress clinical manifestations of experimental autoimmune myasthenia gravis. This demonstrates that use of antibodies against immune response gene products that are associated with susceptibility to disease may be feasible for therapy in autoimmune conditions such as myasthenia gravis.     

Rheumatoid arthritis and myasthenia gravis: a case-based review of the therapeutic options

Clinical Rheumatology - Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction, often associated with other autoimmune diseases, including rheumatoid arthritis. Patients...     

Thymomes et maladies auto-immunes

The association between thymoma and autoimmunity is well known. Besides myasthenia gravis, which is found in 15 to 20% of patients with thymoma, other autoimmune diseases have been reported: erythroblastopenia, systemic lupus erythematosus, inflammatory myopathies, thyroid disorders, Isaac's syndrome or Good's syndrome. More anecdotally, Morvan's syndrome, limbic encephalitis, other autoimmune cytopenias, autoimmune hepatitis, and bullous skin diseases (pemphigus, lichen) have been reported. Autoimmune diseases occur most often before thymectomy, but they can be discovered at the time of surgery or later. Two situations require the systematic investigation of a thymoma: the occurrence of myasthenia gravis or autoimmune erythroblastopenia. Nevertheless, the late onset of systemic lupus erythematosus or the association of several autoimmune manifestations should lead to look for a thymoma. Neither the characteristics of the patients nor the pathological data can predict the occurrence of an autoimmune disease after thymectomy. Thus, thymectomy usefulness in the course of the autoimmune disease, except myasthenia gravis, has not been demonstrated. This seems to indicate the preponderant role of self-reactive T lymphocytes distributed in the peripheral immune system prior to surgery. Given the high infectious morbidity in patients with thymoma, immunoglobulin replacement therapy should be considered in patients with hypogammaglobulinemia who receive immunosuppressive therapy, even in the absence of prior infection.     

Pericarditis in myasthenia gravis

Myasthenia gravis is an autoimmune disorder with antibodies to the acetylcholine receptors (Ach R) in skeletal muscles. Myocardial involvement can present as a myocarditis or with arrhythmias. To our knowledge, there is no documentation in the literature of pericardial involvement in myasthenia gravis. We report the presence of pericardial effusion and atrioventricular conduction block in a patient with myasthenia gravis that responded appropriately to immunosuppressive therapy and plasma exchanges.     

Myasthenia Gravis and Lambert‐Eaton Syndrome

Abstract: Myasthenia gravis is a common autoimmune disorder characterized by the presence of pathogenic antibodies directed against the acetylcholine receptor. Patients present with variable degrees and distribution of fluctuating weakness at times life threatening. Clinical manifestations, establishment of diagnosis, the natural history of myasthenia gravis, and therapeutic options are herein reviewed. Far less common is Lambert‐Eaton syndrome (the myasthenic syndrome), another autoimmune disorder due to the presence of antibodies directed against the PQ‐type voltage‐gated calcium channels. Clinical features and treatment options are summarized.     

Newly diagnosed multiple sclerosis in a patient with ocular myasthenia gravis: A case report

Rationale:Patients with myasthenia gravis may also have comorbid autoimmune diseases. Since both myasthenia gravis and neuromyelitis optica spectrum disease are mediated by antibodies, they are likely to occur together. However, since multiple sclerosis is an autoimmune disease that is not mediated by a specific antibody, it has fewer immune mechanisms in common with myasthenia gravis than neuromyelitis optica spectrum disease. We encountered a case of newly developed multiple sclerosis in a patient with myasthenia gravis.Patient concerns:A 46-year-old man was diagnosed with ocular myasthenia gravis 6 years ago and had been taking pyridostigmine to control his symptoms.Diagnosis:The patient developed right optic neuritis, and multiple sclerosis was suspected based on the brain magnetic resonance imaging findings. However, the required diagnostic criteria were not met.Interventions:Disease-modifying therapy was not initiated, and clinical progression of the disease was monitored.Outcomes:One year after the onset of optic neuritis, the patient developed myelitis and was diagnosed with multiple sclerosis, prompting treatment with disease-modifying therapy.Lessons:When optic neuritis occurs in patients with myasthenia gravis, careful evaluation is necessary while considering the possibility that it may be the first symptom of a demyelinating central nervous system disease. Therefore, it is important to conduct shorter-interval monitoring and symptom screening for patients with neurological autoimmune diseases, such as myasthenia gravis, even if multiple sclerosis is not initially suspected, to achieve early detection of multiple sclerosis.     

Steroids induce acetylcholine receptors on cultured human muscle: implications for myasthenia gravis.

Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. We show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. Our results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also to a direct effect on muscle. We propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.     

Response of myasthenia gravis to rituximab in a patient with non-Hodgkin lymphoma

Myasthenia gravis is a B-cell-mediated autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles. The underlying defect is an autoantibody-mediated attack on the acetylcholine receptors (AchRs) at the neuromuscular junction. Rituximab is a genetically engineered chimeric murine/human monoclonal antibody indicated for treatment of patients with low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphoma. Based on its potential for elimination of auto-reactive B-cell clones, rituximab may have a role in the management of some autoimmune disorders. We report a patient with B-cell, follicular non-Hodgkin lymphoma and a long-standing history of myasthenia gravis and the favorable impact of rituximab on both disorders.     

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.     

Experimentelle Thymitis,Myokarditis und Polymyositis

Zusammenfassung Die Myasthenia gravisErb wird heute auf Grund klinisch-serologischer und pathologisch-anatomischer Befunde zu den Autoimmunkrankheiten gerechnet. Die Versuche einer Reproduktion des Leidens im Experimentaltier haben bisher bezüglich der morphologischen Veränderungen keine zufriedenstellende Ergebnisse gebracht. Bei insgesamt 70 einen Monat alten männlichen Swiss-Mäusen (20 Tiere dienten als Kontrollen) konnte durch die intramuskuläre Injektion von homologem sulfanilsäurediazotiertem Herzmuskelextrakt (2 Injektionen/Woche über 4 Wochen) erstmals das morphologische Äquivalent einer Myasthenia gravis erzeugt werden. 45% der Tiere entwickelten lymphoepitheliale Follikel im Thymusmark, in Herzmuskel (68% der Tiere), Zwerchfell (40%) und Psoas (18%) traten teils perivaskulär, teils interstitiell lympho-histiozytäre Infiltrate auf, welche bei 6 Tieren so ausgedehnt waren daß von einer diffusen Myokarditis und Polymyositis mit Muskelfasernekrosen gesprochen werden kann. Die Befunde lassen erkennen, daß bei der Myasthenia gravis Autoimmunphaenomenen entscheidende pathogenetische Bedeutung zumindest für die hierbei darstellbaren pathologisch-anatomischen Veränderungen zukommt.

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Summary Clinical, serological and morphological aspects indicate that myasthenia gravis is consistent with disorders of autoimmune etiology. Experimental efforts to reproduce this disease in experimental animals have until now brought contradictory results especially concerning the morphological alterations in thymus and striated muscle. In at all 70 one month old male swiss mice (20 mice served as controls) we succeeded in producing the morphological aequivalents of myasthenia gravis by the i.m. application of homologous heart muscle extract diazotised with sulfanilic acid (2 injections/week over a 4 week period). 45% of the immuzed animals developed lympho-epithelial follikular structures in the thymic medulla; in heart muscle (68%), diaphragm (48%) and psoas muscle (18%) emerged lymphohistiocytic infiltrations, which were in part perivasculary in part interstitially situated and could not be seen in controls. 6 animals out of these had severe diffuse lympho-histiocytic myocarditis and polymyositis with muscle fiber necrosis. These results indicate that in myasthenia gravis autoimmune phenomena play an important role as pathogenetic mechanismus at least concerning the pathoanatomical findings of this disease in man.

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Mit 3 Abbildungen in 6 Einzeldarstellungen     

Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis

Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a glutenfree diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 （or, about 4.3%） was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.     

Concomitant polymyositis and myasthenia gravis reveal malignant thymoma. A case report and review of the literature.

The frequency of thymona associated with autoimmune diseases has been reported to be increased, with 50% of thymoma patients also having myasthenia gravis (MG). Other autoimmune disorders, such as autoimmune erythroblastopenia and polymyositis (PM), have been less frequently associated with thymoma. The association of MG and PM with thymoma is rare. We here report the case of a 66-year-old woman whose concomitant MG and PM revealed malignant thymoma and review the other published cases of this association.     

Involvement of human muscle acetylcholine receptor alpha-subunit gene (CHRNA) in susceptibility to myasthenia gravis.

The muscle acetylcholine receptor is the major target of the autoimmune response in generalized myasthenia gravis. To investigate the role of the gene encoding the alpha subunit of the receptor (CHRNA), two stable polymorphic d[(GT).(CA)]dinucleotide repeats, designated HB and BB, were characterized within the first intron of CHRNA. The HB*14 allele conferred a relative risk for myasthenia gravis of 2.5 in 81 unrelated patients compared with 100 control subjects. Very significantly, family analysis based on haplotype segregation data indicated that parental haplotypes associated with HB*14 always segregated to the child with myasthenia gravis (P < 0.0002 for the comparison with the transmission of haplotypes not bearing HB*14), whereas their transmission to unaffected siblings was equilibrated. Myasthenia gravis patients also showed a high frequency of microsatellite variants unseen in controls. These findings implicate the CHRNA in susceptibility to myasthenia gravis.     

Myasthenia gravis and elderly persons. A case study]

INTRODUCTION: Myasthenia gravis is an uncommon autoimmune disease which affects all ages. There are late-onset occurrences whose diagnosis is not considered often enough in geriatrics. EXEGESIS: We report a case of late-onset myasthenia gravis with a 78-year-old woman who was multi-pathologic and hospitalized for a diplopia check-up and recurrent falls. These stress the difficulty of suggesting myasthenia gravis in geriatrics due to the number of differential diagnoses that can mislead the physician. For the elderly subject, the diagnostic methodology is close to that of the younger subject. The search for related diseases must be systematic. CONCLUSION: Late-onset myasthenia gravis must remain a diagnosis present in the mind of the physician because of the significant improvement of the functional prognosis after the start of the treatment. The majority of subjects will recover a normal life.