Chapter category: Autoimmunity
CTLA-4 in Myasthenia Gravis
CTLA-4 in Autoimmune Disease
Edited by: Flemming PociotISBN: 1-58706-068-X
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Chapter authors:
Ann Kari Lefvert
Myasthenia gravis (MG) is commonly regarded as the prototype for an organ specific antibody-mediated autoimmune disease. The disease is characterized by an immune response against the nicotinic acetylcholine receptor on the neuromuscular junction. The symptoms, weakness and increased fatigability, are considered to be caused by direct blockade and a reduction in the number of functional receptors at the neuromuscular junction by the autoantibodies.1 The poor correlation between the autoantibody concentration and the disease severity challenges the concept of a simple cause and effect relationship between these antibodies and the disease. Moreover, acetylcholine receptor antibodies are found in several conditions not accompanied by neuromuscular symptoms, including some thymomas,2 healthy first-degree relatives3 and in the healthy twin in a monozygotic pair of twins discordant for MG,4 in monoclonal gammopathies5 and in primary biliary cirrhosis.6 Recent reports suggest that proinflammatory cytokines, such as IL-1 and tumor necrosis factor TNF, may play a more direct role in the development of the disease and its symptoms. Transgenic mice that express IFN-• at the neuromuscular junction, develop a myasthenia-like disease.7 Patients with MG, especially those with no HLA-B8 association, have a rather strong genetic association to high-secretory genotype A2 of IL-1•,8 and to the high-secretory genotype A2 of TNF-•.9 Animal experiments have supported the important role of IL-1•. Mice deficient of IL-1• have a much-reduced incidence and disease-severity of experimental myasthenia gravis induced by acetylcholine receptor. In these mice, both T- and B- cell responses to the receptor are reduced.10
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CTLA-4 in Myasthenia Gravis
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Myasthenia gravis (MG) is commonly regarded as the prototype for an organ specific antibody-mediated autoimmune disease. The disease is characterized by an immune response against the nicotinic acet...
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