Anti-TNF-α Antibodies Suppress the Development of Experimental Autoimmune Myasthenia Gravis

Duan, Rui‐Sheng; Wang, Huabing; Yang, Jiangning; Scallon, Bernie; Link, Hans; Xiao, Bao‐Guo

doi:10.1006/jaut.2002.0618

Cited by 43 publications

(36 citation statements)

References 33 publications

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“…CD4 ϩ Th1 cells are known to be involved in the development of EAMG, promoting the synthesis of anti-AChR Abs that bind and activate complement and cause destruction of the NMJ (39 -41). IFN-␥ and TNF-␣ are Th1, proinflammatory cytokines known to be crucial to the induction and development of EAMG (13,(42)(43)(44). Furthermore, the Th2 cytokine, IL-4, may have a protective role in EAMG as mice deficient in IL-4 are more susceptible to EAMG induction (45).…”

Section: Discussionmentioning

confidence: 99%

Suppression of Experimental Autoimmune Myasthenia Gravis by Granulocyte-Macrophage Colony-Stimulating Factor Is Associated with an Expansion of FoxP3+ Regulatory T Cells

Sheng

Ganesh

et al. 2006

The Journal of Immunology

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Dendritic cells (DCs) have the potential to activate or tolerize T cells in an Ag-specific manner. Although the precise mechanism that determines whether DCs exhibit tolerogenic or immunogenic functions has not been precisely elucidated, growing evidence suggests that DC function is largely dependent on differentiation status, which can be manipulated using various growth factors. In this study, we investigated the effects of mobilization of specific DC subsets—using GM-CSF and fms-like tyrosine kinase receptor 3-ligand (Flt3-L)—on the susceptibility to induction of experimental autoimmune myasthenia gravis (EAMG). We administered GM-CSF or Flt3-L to C57BL/6 mice before immunization with acetylcholine receptor (AChR) and observed the effect on the frequency and severity of EAMG development. Compared with AChR-immunized controls, mice treated with Flt3-L before immunization developed EAMG at an accelerated pace initially, but disease frequency and severity was comparable at the end of the observation period. In contrast, GM-CSF administered before immunization exerted a sustained suppressive effect against the induction of EAMG. This suppression was associated with lowered serum autoantibody levels, reduced T cell proliferative responses to AChR, and an expansion in the population of FoxP3+ regulatory T cells. These results highlight the potential of manipulating DCs to expand regulatory T cells for the control of autoimmune diseases such as MG.

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Section: Discussionmentioning

confidence: 99%

Suppression of Experimental Autoimmune Myasthenia Gravis by Granulocyte-Macrophage Colony-Stimulating Factor Is Associated with an Expansion of FoxP3+ Regulatory T Cells

Sheng

Ganesh

et al. 2006

The Journal of Immunology

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“…Other studies demonstrated the important role of Th1 cells in EAMG by changing the concentration of Th1 cytokines in rodents with normal genes for cytokines and their receptors. For example, treatment of rats with anti-TNF-α Abs suppresses EAMG development (58), and treatment of mice with a soluble recombinant form of the human TNF receptor, able to outcompete mouse TNF-α for binding to the mouse receptor, significantly improves symptoms of established EAMG (59). Moreover, estrogen enhances EAMG development in mice by promoting augmented IL-12 production by AChR-specific Th1 cells, suggesting that estrogens mediate sex differences in autoimmunity because of a Th1-mediated mechanism (60) (Figure 3).…”

Section: Role Of Cd4 + T Cells In Mg Pathogenic Anti-achrmentioning

confidence: 99%

Myasthenia gravis: past, present, and future

Conti‐Fine

Milani²,

Kaminski³

2006

J. Clin. Invest.

560

512

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Pathogenesis of MG: current state of the artStructure and function of the NMJ. The terminal arborization of α-motor neuron axons from the ventral horns of the spinal cord and brainstem provides the nerve terminals that form the NMJ (Figure 1). These myelinated axons reach the muscles through peripheral nerves; then each axon divides into branches that innervate many individual muscle fibers. As it approaches its target fiber, each branch loses the myelin sheath and further subdivides into many presynaptic boutons, which contain ACh-loaded synaptic vesicles and face the surface of the muscle fiber at the NMJ ( Figure 1). The synaptic bouton and the muscle surface are separated by the synaptic cleft, a 20 nm-thick space that contains acetylcholinesterase (AChE) and other proteins and proteoglycans involved in

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“…Anti-inflammatory treatment lowers the levels of complement-fixing antibodies (IgG, IgG 2a and IgG 2b ) and decreases the affinity of anti-AChR IgG. Treatment with anti-TNF-α antibodies can suppress the induction and development of EAMG [82]. Comparable results were obtained with experimental treatment with human recombinant IL-1 receptor antagonist (IL-1ra).…”

Section: Complement and Cytokine Regulationmentioning

confidence: 99%

Effect of complement and its regulation on myasthenia gravis pathogenesis

Kusner¹,

Kaminski²,

Šoltýs³

2008

Expert Review of Clinical Immunology

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Myasthenia gravis (MG) is primarily caused by antibodies directed towards the skeletal muscle acetylcholine receptor, leading to muscle weakness. Although these antibodies may induce compromise of neuromuscular transmission by blocking acetylcholine receptor function or antigenic modulation, the predominant mechanism of injury to the neuromuscular junction is complement-mediated lysis of the postsynaptic membrane. The vast majority of data to support the role of complement derives from experimentally acquired MG (EAMG). In this article, we review studies that demonstrate the central role of complement in EAMG and MG pathogenesis along with the emerging role of complement in T-and B-cell function, as well as the potential for complement inhibitor-based therapy to treat human MG.

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Anti-TNF-α Antibodies Suppress the Development of Experimental Autoimmune Myasthenia Gravis

Cited by 43 publications

References 33 publications

Suppression of Experimental Autoimmune Myasthenia Gravis by Granulocyte-Macrophage Colony-Stimulating Factor Is Associated with an Expansion of FoxP3+ Regulatory T Cells

Suppression of Experimental Autoimmune Myasthenia Gravis by Granulocyte-Macrophage Colony-Stimulating Factor Is Associated with an Expansion of FoxP3+ Regulatory T Cells

Myasthenia gravis: past, present, and future

Effect of complement and its regulation on myasthenia gravis pathogenesis

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