Animal Models of Myasthenia Gravis

Christadoss, Premkumar; Poussin, Mathilde; Deng, Cheng

doi:10.1006/clim.1999.4807

Cited by 143 publications

(56 citation statements)

References 98 publications

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“…The advantages of using the EAMG model is that it mimics the human disease in terms of immuopathologic and clinical manifestations [19,20]. Moreover, it is widely used for determining efficacy of potential therapeutic strategies [18-20].…”

Section: Methodsmentioning

confidence: 99%

Rapamycin alleviates inflammation and muscle weakness, while altering the Treg/Th17 balance in a rat model of myasthenia gravis

et al. 2017

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Myasthenia gravis (MG) is an autoimmune disease commonly treated with immunosuppressants. We evaluated the novel immunosuppressant, rapamycin (RAPA), in a rat model of experimental autoimmune MG (EAMG). Mortality rates in the RAPA (12%) were significantly down compared with the EAMG (88%) or cyclophosphamide (CTX) (68%) intervention groups. Muscular weakness decreased after both RAPA and CTX treatment. However, Lennon scores were lower (1.74 ± 0.49, 3.39 ± 0.21, and 3.81 ± 0.22 in RAPA, CTX, and EAMG groups, respectively), and body weights (203.12 ± 4.13 g, 179.23 ± 2.13 g, and 180.13 ± 5.13 g in RAPA, CTX, and EAMG groups, respectively) were significantly higher, only in the RAPA group. The proportion of regulatory T cells (Treg) significantly increased, while that of Th17 cells significantly decreased in the RAPA group compared with the EAMG group. In comparison, CTX intervention resulted in increased Th17 but significantly decreased Tregs. Hence, RAPA can be more effectively used in comparison with CTX to treat MG, with an efficacy higher than that of CTX. In addition, our results suggest RAPA’s efficacy in alleviating symptoms of MG stems from its ability to correct the Treg/Th17 imbalance observed in MG.

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Section: Methodsmentioning

confidence: 99%

Rapamycin alleviates inflammation and muscle weakness, while altering the Treg/Th17 balance in a rat model of myasthenia gravis

et al. 2017

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“…A mouse model of experimental autoimmune MG (EAMG), which mimics MG, is induced by immunizing mice 2–3 times with Torpedo AChR in CFA (Christadoss et al, 2000). The predominant anti-AChR Ig isotype that develops after two immunizations of these mice is IgG2b, followed by IgG1 (Allman et al, 2011), which have features in common with human IgG1 and IgG4, respectively (Hussain and Kifayet, 1995; Nimmerjahn and Ravetch, 2010).…”

Section: Introductionmentioning

confidence: 99%

IgG1 deficiency exacerbates experimental autoimmune myasthenia gravis in BALB/c mice

Huda

Strait

Tüzün

et al. 2015

Journal of Neuroimmunology

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Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to neuromuscular junction (NMJ) damage by anti-acetylcholine receptor (AChR) auto-antibodies and complement. In experimental autoimmune myasthenia gravis (EAMG), which is induced by immunization with Torpedo AChR in CFA, anti-AChR IgG2b and IgG1 are the predominant isotypes in the circulation. Complement activation by isotypes such as IgG2b plays a crucial role in EAMG pathogenesis; this suggested the possibility that IgG1, which does not activate complement through the classical pathway, may suppress EAMG. In this study, we show that AChR-immunized BALB/c mice genetically deficient for IgG1 produce higher levels of complement-activating isotypes of anti-AChR, especially IgG3 and IgG2a, and develop increased IgG3/IgG2a deposits at the NMJ, as compared to wild type (WT) BALB/c mice. Consistent with this, AChR-immunized IgG1−/− BALB/c mice lose muscle strength and muscle AChR to a greater extent than AChR-immunized WT mice. These observations demonstrate that IgG1 deficiency leads to increased severity of EAMG associated with an increase in complement activating IgG isotypes. Further studies are needed to dissect the specific role or mechanism of IgG1 in limiting EAMG and that of EAMG exacerbating role of complement activating IgG3 and IgG2a in IgG1 deficiency.

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“…The AChR antibodies of patients are polyclonal and recognize a complex repertoire of epitopes that differ among individual patients. Experimentally acquired myasthenia gravis (EAMG) produced by administration of purified AChR to rodents has similar immune characteristics to the human disease [25], [26]. Studies that highlight the mechanisms involved in driving the autoimmune process have largely focused on the complexity of the breakdown of tolerance [27] but have not addressed in detail the mechanisms by which autoreactive B cells may escape programmed cell death.…”

Section: Introductionmentioning

confidence: 99%

Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study

et al. 2014

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The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders.

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Animal Models of Myasthenia Gravis

Cited by 143 publications

References 98 publications

Rapamycin alleviates inflammation and muscle weakness, while altering the Treg/Th17 balance in a rat model of myasthenia gravis

Rapamycin alleviates inflammation and muscle weakness, while altering the Treg/Th17 balance in a rat model of myasthenia gravis

IgG1 deficiency exacerbates experimental autoimmune myasthenia gravis in BALB/c mice

Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study

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