Anti-TNF-alpha antibodies suppress the development of experimental autoimmune myasthenia gravis

Rui-Sheng Duan1, Hua-Bing Wang, Jian-She Yang

  • 1Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.

Journal of Autoimmunity
|December 11, 2002
PubMed

To understand the role of TNF-alpha in the induction of experimental autoimmune myasthenia gravis (EAMG) and detect a possible effect of anti-TNF-alpha antibodies in the treatment of EAMG, anti-TNF-alpha antibodies were administrated intraperitoneally to Lewis rats twice per week for 5 weeks from the day of immunization with Torpedo AChR and complete Freund's adjuvant (CFA). Administration of anti-TNF-alpha antibodies resulted in lower incidence of EAMG, and in delayed onset and only mild muscle weakness compared with control EAMG rats. These mild clinical signs were accompanied by lower AChR-specific lymphocyte proliferation, down-regulated IFN-gamma and IL-10, and up-regulated TGF-beta. The lower levels of anti-AChR IgG, Ig2a and IgG2b and decreased anti-AChR IgG affinity were found in rats treated with anti-TNF-alpha antibodies. These results demonstrate that anti-TNF-alpha antibodies can suppress the induction and development of EAMG.

Related Concept Videos

Myasthenia Gravis: Overview and Treatment01:20

Myasthenia Gravis: Overview and Treatment

Myasthenia gravis is a neuromuscular transmission disorder characterized by weakness and increased fatigability of skeletal muscles. It is an autoimmune disease affecting approximately one in 2000 people, where antibodies against the α1 subunit of nicotinic acetylcholine receptors are produced.
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which leads...
Myasthenia Gravis ll: Pathophysiology01:22

Myasthenia Gravis ll: Pathophysiology

The disease process of myasthenia gravis begins at the neuromuscular junction, where antibodies attack key proteins needed for muscle activation. This immune reaction weakens signal transmission, leading to the characteristic muscle fatigue and weakness that define the condition.Immune-Mediated DamageIn most individuals, antibodies target acetylcholine receptors (AChRs) on the postsynaptic membrane of muscle cells. By blocking acetylcholine binding, these antibodies prevent the nerve signal...
Myasthenia Gravis: Diagnostic Tests01:15

Myasthenia Gravis: Diagnostic Tests

Myasthenia gravis is an autoimmune condition affecting neuromuscular transmission, causing generalized weakness in skeletal muscles. Initial diagnoses rely on patients' signs, symptoms, and medical history. The challenge lies in distinguishing myasthenia from other muscular dystrophies. An important diagnostic feature is the significant improvement of symptoms after administering anticholinesterase inhibitors.
The edrophonium test is a diagnostic tool for myasthenia gravis. It involves...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Chemical Synapses01:26

Chemical Synapses

Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...