Roles of cytokines and T cells in the pathogenesis of myasthenia gravis

Uzawa, Akiyuki; Kuwabara, Satoshi; Suzuki, Shigeaki; Imai, Tomihiro; Murai, Hiroyuki; Ozawa, Yukiko; Yasuda, Manato; Nagane, Yuriko; Utsugisawa, Kimiaki

doi:10.1111/cei.13546

Cited by 89 publications

(59 citation statements)

References 74 publications

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“…Multiple mechanisms are implicated, including the release of interleukin 17 (IL-17), among other cytokines, which indirectly promote immunoglobulin production. Th17 cells also affect the balance of the cytokine profile of Th1 and Th2 cells, thus influencing antibody production [ 118 ]. Several studies have shown that patients with MG have elevated levels of Th17 cells and IL-17, which correlate with disease severity and antibody titers [ 119 , 120 ].…”

Section: Pathophysiologymentioning

confidence: 99%

Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations

Dresser

Wlodarski

Rezania

et al. 2021

JCM

216

130

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Myasthenia gravis (MG) is an autoimmune neurological disorder characterized by defective transmission at the neuromuscular junction. The incidence of the disease is 4.1 to 30 cases per million person-years, and the prevalence rate ranges from 150 to 200 cases per million. MG is considered a classic example of antibody-mediated autoimmune disease. Most patients with MG have autoantibodies against the acetylcholine receptors (AChRs). Less commonly identified autoantibodies include those targeted to muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (Lrp4), and agrin. These autoantibodies disrupt cholinergic transmission between nerve terminals and muscle fibers by causing downregulation, destruction, functional blocking of AChRs, or disrupting the clustering of AChRs in the postsynaptic membrane. The core clinical manifestation of MG is fatigable muscle weakness, which may affect ocular, bulbar, respiratory and limb muscles. Clinical manifestations vary according to the type of autoantibody, and whether a thymoma is present.

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Section: Pathophysiologymentioning

confidence: 99%

Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations

Dresser

Wlodarski

Rezania

et al. 2021

JCM

216

130

View full text Add to dashboard Cite

show abstract

“…The immune system is a critical regulator of both neurological ( Prinz and Priller, 2017 ) and muscular ( Farup et al, 2015 ) homeostasis, injury response, and pathology. The chronic injury cycles characteristic of multiple NMDs result in persistent and increased infiltration of monocytes/macrophages ( Acharyya et al, 2007 ), T lymphocytes ( Uzawa et al, 2021 ), and mast cells ( Trias et al, 2017 ) at NMJs. These cells secrete multiple factors that induce a chronic pro-inflammatory environment and contribute to disease progression through several mechanisms that increase oxidative stress and alter stem cell function.…”

Section: Discussionmentioning

confidence: 99%

Neuromuscular Development and Disease: Learning From in vitro and in vivo Models

Fralish

Lotz

Chavez

et al. 2021

Front. Cell Dev. Biol.

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The neuromuscular junction (NMJ) is a specialized cholinergic synaptic interface between a motor neuron and a skeletal muscle fiber that translates presynaptic electrical impulses into motor function. NMJ formation and maintenance require tightly regulated signaling and cellular communication among motor neurons, myogenic cells, and Schwann cells. Neuromuscular diseases (NMDs) can result in loss of NMJ function and motor input leading to paralysis or even death. Although small animal models have been instrumental in advancing our understanding of the NMJ structure and function, the complexities of studying this multi-tissue system in vivo and poor clinical outcomes of candidate therapies developed in small animal models has driven the need for in vitro models of functional human NMJ to complement animal studies. In this review, we discuss prevailing models of NMDs and highlight the current progress and ongoing challenges in developing human iPSC-derived (hiPSC) 3D cell culture models of functional NMJs. We first review in vivo development of motor neurons, skeletal muscle, Schwann cells, and the NMJ alongside current methods for directing the differentiation of relevant cell types from hiPSCs. We further compare the efficacy of modeling NMDs in animals and human cell culture systems in the context of five NMDs: amyotrophic lateral sclerosis, myasthenia gravis, Duchenne muscular dystrophy, myotonic dystrophy, and Pompe disease. Finally, we discuss further work necessary for hiPSC-derived NMJ models to function as effective personalized NMD platforms.

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“…Although the actual underlying mechanisms of MG are unclear, presence of ectopic germinal centers (GCs) and loss of central as well as peripheral tolerance have been discussed (1). High numbers of Th17 cells, follicular Th (Tfh) cells, and dysfunction of Tregs have been shown to promote autoantibody production from B cells and plasma cells (PCs), thereby exacerbating MG pathogenesis (45). Interestingly, the pattern of MG pathogenesis, to some extent, overlaps with the underlying mechanism of vaccine action.…”

Section: Mechanism Of Vaccination and Mgmentioning

confidence: 99%

“…Interestingly, the pattern of MG pathogenesis, to some extent, overlaps with the underlying mechanism of vaccine action. For example, Tfh cells are required for GCs, Abs, and long-lived PC responses, not only in MG but also in vaccine immunization (45,46). Nonetheless, the link between the underlying mechanism of vaccination action and MG remains unclear.…”

Section: Mechanism Of Vaccination and Mgmentioning

confidence: 99%

To Be or Not To Be Vaccinated: That Is a Question in Myasthenia Gravis

Zhou

Yang

et al. 2021

Front. Immunol.

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Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and abnormal fatigability due to the antibodies against postsynaptic receptors. Despite the individual discrepancy, patients with MG share common muscle weakness, autoimmune dysfunction, and immunosuppressive treatment, which predispose them to infections that can trigger or exacerbate MG. Vaccination, as a mainstay of prophylaxis, is a major management strategy. However, the past years have seen growth in vaccine hesitancy, owing to safety and efficacy concerns. Ironically, vaccines, serving as an essential and effective means of defense, may induce similar immune cross-reactivity to what they are meant to prevent. Herein, we outline the progress in vaccination, review the current status, and postulate the clinical association among MG, vaccination, and immunosuppression. We also address safety and efficacy concerns of vaccination in MG, in relation to COVID-19. Since only a handful of studies have reported vaccination in individuals with MG, we further review the current clinical studies and guidelines in rheumatic diseases. Overall, our reviews offer a reference to guide future vaccine clinical decision-making and improve the management of MG patients.

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Roles of cytokines and T cells in the pathogenesis of myasthenia gravis

Cited by 89 publications

References 74 publications

Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations

Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations

Neuromuscular Development and Disease: Learning From in vitro and in vivo Models

To Be or Not To Be Vaccinated: That Is a Question in Myasthenia Gravis

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