Myasthenia gravis following Viral Infection

Korn, Isabelle Lubetzki; Abramsky, Oded

doi:10.1159/000115275

Cited by 25 publications

(4 citation statements)

References 15 publications

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“… Excess production of a highly specific pathogenic IgG autoantibody by autoreactive B2 cell clones as, for example, in myasthenia gravis ( 108 ). Expansion of such B2 cell clones could have been driven by antigen, e.g., with cross-reactive micro-organisms in patients without thymoma ( 109 ) or be driven by acetylcholine receptor specific autoreactive helper CD4 + T cells in thymoma-associated myasthenia gravis where such autoreactive T cells have escaped tolerance mechanisms ( 110 , 111 ). Deficiency of IgM-NAA, especially IgM-NAA with anti-idiotypic activity to a specific IgG autoantibody, thus incompletely neutralizing the increase in pathogenic IgG autoantibodies, such as antibodies to neutrophil cytoplasmic enzymes (myeloperoxidase, proteinase 3), which are commonly referred to as ANCA, dsDNA, and glomerular basement membrane (GBM) that are present in normal individuals ( 31 , 50 , 87 , 112 ).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of Natural Autoantibodies and Natural IgM Anti-Leucocyte Autoantibodies in Health and Disease

Lobo

2016

Front. Immunol.

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We review how polyreactive natural IgM autoantibodies (IgM-NAA) protect the host from invading micro-organisms and host neo-antigens that are constantly being produced by oxidation mechanisms and cell apoptosis. Second, we discuss how IgM-NAA and IgM anti-leukocyte antibodies (IgM-ALA) inhibits autoimmune inflammation by anti-idiotypic mechanisms, enhancing removal of apoptotic cells, masking neo-antigens, and regulating the function of dendritic cells (DC) and effector cells. Third, we review how natural IgM prevents autoimmune disorders arising from pathogenic IgG autoantibodies, triggered by genetic mechanisms (e.g., SLE) or micro-organisms, as well as by autoreactive B and T cells that have escaped tolerance mechanisms. Studies in IgM knockout mice have clearly demonstrated that regulatory B and T cells require IgM to effectively regulate inflammation mediated by innate, adaptive, and autoimmune mechanisms. It is, therefore, not surprising why the host positively selects such autoreactive B1 cells that generate IgM-NAA, which are also evolutionarily conserved. Fourth, we show that IgM-ALA levels and their repertoire can vary in normal humans and disease states and this variation may partly explain the observed differences in the inflammatory response after infection, ischemic injury, or after a transplant. We also show how protective IgM-NAA can be rendered pathogenic under non-physiological conditions. We also review IgG-NAA that are more abundant than IgM-NAA in plasma. However, we need to understand if the (Fab)2 region of IgG-NAA has physiological relevance in non-disease states, as in plasma, their functional activity is blocked by IgM-NAA having anti-idiotypic activity. Some IgG-NAA are produced by B2 cells that have escaped tolerance mechanisms and we show how such pathogenic IgG-NAA are regulated to prevent autoimmune disease. The Fc region of IgG-NAA can influence inflammation and B cell function in vivo by binding to activating and inhibitory FcγR. IgM-NAA has therapeutic potential. Polyclonal IgM infusions can be used to abrogate on-going inflammation. Additionally, inflammation arising after ischemic kidney injury, e.g., during high-risk elective cardiac surgery or after allograft transplantation, can be prevented by pre-emptively infusing polyclonal IgM or DC pretreated ex vivo with IgM or by increasing in vivo IgM with a vaccine approach. Cell therapy is appealing as less IgM will be required.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Natural Autoantibodies and Natural IgM Anti-Leucocyte Autoantibodies in Health and Disease

Lobo

2016

Front. Immunol.

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“…(4)(5)(6)(7)(8) Extensive review of the literature revealed cases of MG following viral infections. (9)(10)(11)(12)(13)(14)(15) This case, to the best of our knowledge, is the first reported case of MG following malaria infection.…”

Section: Introductionmentioning

confidence: 81%

“…A previous study raised the possibility of viral infection as etiological factor for myasthenia gravis and described five myasthenic patients, whose symptoms began a few weeks after a proven viral infection. (9) In addition, two cases of post-infectious myasthenia gravis were reported by Felice and colleagues in 2005 (10) ; a five year old boy who developed oculo-bulbar weakness two weeks following a varicellazoster infection and a four-year-old boy who developed facial diplegia and dysarthria several weeks following a viral pharyngitis. A third case was reported in 2007 by Saha et al representing the youngest, and second reported, case of post-varicella myasthenia gravis.…”

Section: Discussionmentioning

confidence: 99%

Post-malaria Myasthenia Gravis

Musa

Ibrahim

Badi

et al. 2022

kmj

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We report a nine-year-old girl who presented with complete drooping of the left eyelid and restriction ofmedial gaze following an attack of febrile illness. The child was admitted into a rural hospital where shewas misdiagnosed and managed as a case of meningitis. She was referred to a tertiary children hospitalwhen her condition was not improving and where she developed the eye signs. She was diagnosed as a caseof severe malaria which responded well to quinine therapy. In our neurophysiology clinic, examinationrevealed partial unilateral left eye ptosis, weak frontalis, neck flexors, fingers extensors & knee flexors.Her investigations revealed positive neostigmine test, decremental response to repetitive nerve stimulation(-15.6%,nasalis), increased jitter in single-fibre electromyography (left frontalis & extensor-digitorumcommunis) and negative serology for myasthenia gravis antibodies. She showed remarkable improvementafter pyridostigmine therapy which continued for three months. Regular follow-up showed no recurrenceof her symptoms.

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Myasthenia gravis and myasthenic syndromes

Engel

1984

Annals of Neurology

244

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More than a decade ago myasthenic symptoms were observed in rabbits immunized with acetylcholine receptor (AChR) [119] and AChR deficiency was found at the neuromuscular junction in human myasthenia gravis (MG) [36]. By 1977 the autoimmune character of MG and the pathogenic role of AChR antibodies had been established by several measures. These included the demonstration of circulating AChR antibodies in nearly 90% of patients with MG [87], passive transfer with IgG of several features of the disease from human to mouse [149], localization of immune complexes (IgG and complement) on the postsynaptic membrane [30], and the beneficial effects of plasmapheresis [20, 123]. Substantial subsequent progress has occurred in understanding the structure and function of AChR and its interaction with AChR antibodies. The relationships of the concentration, specificities, and functional properties of the antibodies to the clinical state in MG have been carefully analyzed, and the mechanisms by which AChR antibodies impair neuromuscular transmission have been further investigated. The clinical classification of MG has been refined, the role of the thymus gland in the disease has been further clarified, and new information has become available on transient neonatal MG. The prognosis for generalized MG is improving, but there is still no consensus on its optimal management. Novel therapeutic approaches to MG are now being explored in animal models. Recognition of the autoimmune origin of acquired MG also implied that myasthenic disorders occurring in a genetic or congenital setting had a different cause. As a result, a number of congenital myasthenic syndromes have come to be recognized and investigated. Finally, an acquired disorder of neuromuscular transmission different from MG, the Lambert-Eaton myasthenic syndrome, has also been shown to have an autoimmune basis. In this syndrome, active zone particles of the presynaptic membrane are direct or indirect targets of the pathogenic autoantibodies.

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Myasthenia gravis following Viral Infection

Cited by 25 publications

References 15 publications

Role of Natural Autoantibodies and Natural IgM Anti-Leucocyte Autoantibodies in Health and Disease

Role of Natural Autoantibodies and Natural IgM Anti-Leucocyte Autoantibodies in Health and Disease

Post-malaria Myasthenia Gravis

Myasthenia gravis and myasthenic syndromes

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