Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis

2005 ◽  
Vol 18 (5) ◽  
pp. 519-525 ◽  
Author(s):  
Angela Vincent ◽  
Maria Isabel Leite
Keyword(s):  
Autoimmune Disease ◽  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Muscle Specific Kinase

scholarly journals Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis

2021 ◽  
Vol 118 (13) ◽  
pp. e2020635118
Author(s):  
Dana L. E. Vergoossen ◽  
Jaap J. Plomp ◽  
Christoph Gstöttner ◽  
Yvonne E. Fillié-Grijpma ◽  
Roy Augustinus ◽  
...  
Keyword(s):  
Stochastic Process ◽  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Binding Sites ◽  
Antiinflammatory Activity ◽  
Autoimmune Response ◽  
Cross Link ◽  
Muscle Specific Kinase ◽  
Opposing Effects

Human immunoglobulin (Ig) G4 usually displays antiinflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 naturally engages in a stochastic process termed “Fab-arm exchange” in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate that this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis. In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders.

scholarly journals Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice

Brain ◽  
2012 ◽  
Vol 135 (4) ◽  
pp. 1081-1101 ◽  
Author(s):  
Rinse Klooster ◽  
Jaap J. Plomp ◽  
Maartje G. Huijbers ◽  
Erik H. Niks ◽  
Kirsten R. Straasheijm ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Muscle Specific Kinase

scholarly journals Third distant recurrence of benign thymoma in a patient with myasthenia gravis

2019 ◽  
Vol 12 (4) ◽  
pp. e228529
Author(s):  
Justin Tyler Van Backer ◽  
Alex Cedeno-Rodriguez ◽  
John Nabagiez
Keyword(s):  
Autoimmune Disease ◽  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Mediastinal Mass ◽  
Distant Recurrence ◽  
Anterior Mediastinal Mass ◽  
Robotic Platform ◽  
Time Intervals ◽  
Robotic Assisted ◽  
Progressive Weakness

Myasthenia gravis (MG) is an autoimmune disease where antibodies attack the presynaptic terminals at the neuromuscular junction causing progressive weakness. Associated with thymomas, resection can improve symptoms. A 29-year-old woman with MG who underwent two previous thymectomies, at ages 11 and 15 presented 14 years later with recurrent MG symptoms and an anterior mediastinal mass. Robotic-assisted thoracoscopic excision of the mediastinal mass was performed without complications. She recovered well and had improvement of her MG symptoms. Thymectomy can significantly improve symptoms in MG even for patients who do not have a thymoma. Reports of distant benign thymoma recurrence are rare. MG patients require continued monitoring and vigilance, even after thymectomy. Benign thymomas can recur even after significant time intervals, and utilisation of the robotic platform for recurrent thymoma excision is safe, even following two sternotomies. Patient symptoms improve with redo thymectomy.

scholarly journals Myasthenia Gravis—An Analysis of Multimodal Evoked Potentials

2021 ◽  
Vol 11 (8) ◽  
pp. 1057
Author(s):  
Edyta Dziadkowiak ◽  
Marta Waliszewska-Prosół ◽  
Małgorzata Wieczorek ◽  
Joanna Bladowska ◽  
Sławomir Budrewicz ◽  
...  
Keyword(s):  
Nervous System ◽  
Autoimmune Disease ◽  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Evoked Potentials ◽  
Peripheral Nervous System ◽  
Comprehensive Analysis ◽  
Mr Images ◽  
Multimodal Evoked Potentials

Introduction: The aim of this study is a comprehensive analysis of the parameters of exogenous evoked potentials (visual, brainstem auditory, and somatosensory) in patients with myasthenia gravis (MG), a prototype of both neuromuscular junction disease and autoimmune disease. The study also seeks to isolate electrophysiological changes that may indicate disorders within the central and/or peripheral nervous system. Methods: A total of forty-two consecutive patients with myasthenia gravis (24 women, 18 men) were included in the study. All of the patients underwent EP examination. MR images were also analyzed. Results: In the group of MG patients, the latency of P100 (113.9 ± 13.9; p < 0.0001) VEP, wave III (3.92 ± 0.29; p = 0.015), wave V (5.93 ± 0.32; <0.0001), interlatency III–V (2.00 ± 0.12; p < 0.0001), interlatency I–V (4.20 ± 0.28; p < 0.001) BAEP, and all components of SEP (N9, P10, N13, P16, N20, P22) were significantly longer. Mean wave I and V amplitude BAEP were relatively lower. Conclusions: The results of the study suggest the presence of disturbances in the bioelectric activities of the central and peripheral nervous system in MG patients.

scholarly journals Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis

2020 ◽  
Author(s):  
Dana L.E. Vergoossen ◽  
Jaap J. Plomp ◽  
Christoph Gstöttner ◽  
Yvonne E. Fillié-Grijpma ◽  
Roy Augustinus ◽  
...  
Keyword(s):  
Stochastic Process ◽  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Binding Sites ◽  
Autoimmune Disorders ◽  
Autoimmune Response ◽  
Cross Link ◽  
Muscle Specific Kinase ◽  
Opposing Effects

AbstractHuman IgG4 usually displays anti-inflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 antibodies naturally engage in a stochastic process termed Fab-arm exchange in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis (MG). In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a novel pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders.Graphical abstract

scholarly journals The epidemiology of myasthenia gravis

2021 ◽  
Vol 14 (1) ◽  
pp. 7-16
Author(s):  
Ana-Maria Bubuioc ◽  
◽  
◽  
Aigerim Kudebayeva ◽  
Saule Turuspekova ◽  
...  
Keyword(s):  
Risk Factors ◽  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Clinical Presentation ◽  
Epidemiological Data ◽  
Postsynaptic Membrane ◽  
Related Protein ◽  
The Past ◽  
Muscle Specific Kinase ◽  
Receptor Muscle

Neuromuscular junction (NMJ) disorders include several dysfunctions that ultimately lead to muscle weakness. Myasthenia gravis (MG) is the most prevalent NMJ disorder with a highly polymorphic clinical presentation and many different faces. Being an autoimmune disease, MG correlates with the presence of detectable antibodies directed against the acetylcholine receptor, muscle-specific kinase, lipoprotein-related protein 4, agrin, titin, and ryanodine in the postsynaptic membrane at the NMJ. MG has become a prototype serving to understand both autoimmunity and the function of the NMJ better. The aim of this review is to synthesize some of the epidemiological data available. Epidemiological data regarding MG are important for postulating hypotheses regarding its etiology and facilitating the description of MG subtypes. Thus, adequate documentation through broad databases is essential. The incidence and prevalence of MG reported around the globe have been rising steadily and consistently over the past decades. Ethnic aspects, gender-related differences, and environmental risk factors have been described, implying that these might contribute to a specific phenotype, further suggesting that MG may be considered an umbrella term that covers several clinical entities.

scholarly journals Myasthenia Gravis Revealing Hodgkin’s Lymphoma

2021 ◽  
Author(s):  
Jaouad Yousfi ◽  
Fatimazahra Bensalek ◽  
Mouna Zahlane ◽  
Laila Benjilali ◽  
Lamiaa Essaadouni
Keyword(s):  
Autoimmune Disease ◽  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Mixed Cellularity ◽  
History Of ◽  
Receptor Antibodies ◽  
Severe Weakness ◽  
Anti Acetylcholine

Introduction: Myasthenia gravis is a rare autoimmune disease caused by autoantibodies directed against the synapses of the neuromuscular junction. Patient and methods: We report the case of a young patient with myasthenia gravis associated with Hodgkin's lymphoma. Results: A 22-year-old patient presented with a 2-month history of severe weakness associated with muscle fatigability and intermittent ptosis without dysphonia or respiratory signs. Clinical examination revealed generalized myasthenia. The EMG did not show post-synaptic block, and anti-acetylcholine receptor antibodies were elevated at 3 nmol/l (normal ?0.3 nmol/l). CT of the thorax showed an anterior medial mass. Immunohistochemistry of the mass revealed mixed cellularity Hodgkin’s lymphoma. Conclusion: The association of lymphomas with myasthenia gravis has been rarely reported.

scholarly journals Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

2021 ◽  
Vol 11 (8) ◽  
pp. 1035
Author(s):  
Maria Pia Giannoccaro ◽  
Patrizia Avoni ◽  
Rocco Liguori
Keyword(s):  
Potassium Channels ◽  
Neuromuscular Junction ◽  
Calcium Channels ◽  
Myasthenia Gravis ◽  
Neuromuscular Transmission ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Immune Mediated ◽  
Recent Developments ◽  
Myasthenic Syndrome

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.

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