SERUM ACETYLCHOLINE-RECEPTOR ANTIBODIES IN MYASTHENIA GRAVIS* (original) (raw)

Serological and experimental studies in different forms of myasthenia gravis

Annals of the New York Academy of Sciences, 2018

Antibodies to the acetylcholine receptor (AChR) have been recognized for over 40 years and have been important in the diagnosis of myasthenia gravis (MG), and its recognition in patients of different ages and thymic pathologies. The 10-20% of patients who do not have AChR antibodies are now known to comprise different subgroups, the most commonly reported of which is patients with antibodies to muscle-specific kinase (MuSK). The use of cell-based assays has extended the repertoire of antibody tests to clustered AChRs, low-density lipoprotein receptor-related protein 4, and agrin. Autoantibodies against intracellular targets, namely cortactin, titin, and ryanodine receptor (the latter two being associated with the presence of thymoma), may also be helpful as biomarkers in some patients. IgG4 MuSK antibodies are clearly pathogenic, but the coexisting IgG1, IgG2, and IgG3 antibodies, collectively, have effects that question the dominance of IgG4 as the sole pathologic factor in MuSK MG...

The Intrathymic Pathogenesis of Myasthenia Gravis

Clinical and Developmental Immunology, 2004

The thymus is considered to play an important role in the pathogenesis of Myasthenia gravis, an autoimmune disease characterized by antibody-mediated skeletal muscle weakness. However, its role is yet to be defined. The studies described herein summarize our efforts to determine how intrathymic expression of the neuromuscular type of acetylcholine (ACh) receptors is involved in the immunopathogenesis of this autoimmune disease. We review the work characterizing the expression of neuromuscular ACh receptors in the thymus and advance a new hypothesis that examines the intrathymic expression of this autoantigen in disease pathogenesis.

Pathophysiology of Myasthenia Gravis

Seminars in Neurology, 2004

Myasthenia gravis (MG) is arguably the best understood autoimmune disease, and its study has also led to fundamental appreciation of mechanisms of neuromuscular transmission. MG is caused by antibodies against the acetylcholine receptor (AChR), which produce a compromise in the end-plate potential, reducing the safety factor for effective synaptic transmission. It is clear that AChR antibody destruction of the postsynaptic surface is dependent on complement activation. A muscle-specific kinase has been recently found to be an antigenic target in MG patients without antibodies against the AChR. Autoantibody production in MG is a T-cell-dependent process, but how a breakdown in tolerance occurs is not known. In MG there is an interesting differential involvement of muscle groups, in particular, the extraocular muscles. This article reviews normal neuromuscular transmission, mechanisms of the autoimmune process of MG, and differential susceptibility of eye muscles to MG.

Experimental myasthenia gravis. A murine system

Journal of Experimental Medicine, 1980

Mice from eight inbred strains were immunized with acetylcholine receptor (AChR) purified from Torpedo californica. All mice developed high concentrations of serum antibodies (10(-6) M) against the immunogen and approximately 80% possessed antibodies reactive with mouse nicotinic AChR. 33% of the mice immunized (n = 236) developed muscular weakness and flaccid paralysis. Behavioral, electrophysiological, and pharmacological similarities were found between the experimentally induced muscular weakness and the disease myasthenia gravis. Susceptibility to experimental myasthenia was found to be strain dependent in that the frequency of paralysis was much greater in some strains than others. The occurrence of muscular weakness and flaccid paralysis did not correlate with the concentration of antibodies reactive with T. californica or mouse AChR. Anti-receptor antibodies which increased the rate of AChR degradation on the mouse muscle cell line, BC3H-1, were found in the serum of both mya...

Antibodies not directed against the acetylcholine receptor in myasthenia gravisAn immunoblot study

Journal of Neuroimmunology, 1987

Sera of 45 patients with myasthenia gravis (MG) and of 30 healthy controls were screened for antibodies against muscle antigens in an immunoblotting solid-phase assay using a preparation of human amputated muscle as the substrate. In each group, the sera showed several bands on the blots. The findings are thought to indicate that antibodies against muscle components are normally present in human sera. Sera from patients or controls could be distinguished by differences in the band staining pattems. It is suggested that antibodies which are not directed against the acetylcholine receptor may nonetheless play an important role in the pathogenesis and clinical course of myasthenia gravis.

Morphological effects of myasthenia gravis patient sera on human muscle cells

Muscle & Nerve, 2006

Myasthenia gravis (MG) is caused primarily by autoantibodies against the nicotinic acetylcholine receptor (AChR), but autoantibodies to other muscle proteins may be present. Many of these proteins have structural or signalling functions, the disruption of which may affect muscle cell morphology or viability. In order to investigate the role of such autoantibodies in MG, we examined the effect of MG patient sera, of different autoantibody composition and obtained at different stages of disease severity, on primary human muscle cells. Sera from MG patients induced changes in cell morphology from typical elongated cells to an irregular phenotype, caused the formation of inclusion bodies and intracellular vesicles, and led to a disordered arrangement of actin microfilaments. Sera from the most severely affected patients also induced cell death, which did not occur via classic apoptosis. The effects were not complement-mediated and were dose-and time-dependent. As the effects observed in the cell culture system correlated with disease severity, a greater understanding of the individual factors responsible for these effects may improve our understanding of MG pathogenesis and be of value in the assessment of disease in individual patients.

Clinical and scientific aspects of acetylcholine receptor myasthenia gravis

Curr Opin Neurol, 2014

Purpose of review Myasthenia gravis is a rare disease that causes impairment of the neuromuscular junction. In this review we will focus on the literature published in the last 18 months regarding autoimmune myasthenia gravis caused by antibodies against the nicotinic acetylcholine receptor myasthenia gravis. Acetylcholine receptor is the most common target of this autoimmune disease. Recent findings A high number of long-lived plasma cells are present in myasthenia gravis patients. Treatments to eliminate these plasma cells, such as proteasome inhibitors, have proved utility in experimental autoimmune myasthenia gravis. MicroRNAs may have a role as biomarkers in myasthenia gravis. Epstein-Barr virus and human polyomavirus 7 are often found in myasthenia gravis thymus and may play a role in the initiation of the autoimmune process. Robotic thymectomy has been proved well tolerated and minimally invasive for the patients and is likely to replace open surgery. Summary Knowledge of the initiation and perpetuation of the autoimmune response in myasthenia gravis condition is increasing every year. This knowledge is paired with in-vivo and in-vitro studies that are directed to further understand this disease, and to improve current treatment options in severe or nonresponding patients. Specific treatments and diagnosis in myasthenia gravis tend to an early detection and a better quality of life.

Aspects of Lymphocyte Function in Myasthenia Gravis*

Annals of the New York Academy of Sciences, 1976

Immunologic abnormalities in myasthenia gravis have been the focus of much attention since the early 1960s. As is evident from the number of papers related to clinical and experimental immunology in this volume, the role of the immune system in myasthenia gravis is still a promising area of research into the pathogenesis of this disorder. Immunologic abnormalities reported in the past in myasthenia gravis have included (1) the presence of antibodies to muscle structural proteins 1-4 and more recently, to muscle acetylcholine receptors 5 9 6 ; (2) evidence both for and against immunodeficiency 7-11; (3) the presence of immunologic activity, * This work was supported in part by United States Public Health Service Grants No. K07-NS11061-03, T01A1-00319, NS-11766, Veterans Administration Grant No. 642-0030, and the Muscular Dystrophy Associations of America.