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Pathogenesis of Myositis and Myasthenia Associated with Titin and Ryanodine Receptor Antibodies
Department of Neurology, University of Bergen, Bergen, Norway
Address for correspondence: Dr. Geir Olve Skeie, Department of Neurology, Haukeland University Hospital, N-5021 Bergen, Norway. Voice: +47-55-97-50-45; fax: +47-55-97-51-65. gske{at}haukeland.no Ann. N.Y. Acad. Sci. 998: 343-350 (2003).
Some myasthenia gravis (MG) patients have antibodies against skeletal muscle antigens in addition to the acetylcholine receptor (AChR). Two major antigens for these antibodies are the Ca2+ release channel of the sarcoplasmic reticulum, the ryanodine receptor (RyR), and titin, a gigantic filamentous muscle protein essential for muscle structure, function, and development. RyR and titin antibodies are found in MG patients with a thymoma and in a proportion of late-onset MG, and they correlate with severe MG disease. The RyR antibodies recognize a region near the N-terminus important for channel regulation. They inhibit Ca2+ release from sarcoplasmic reticulum in vitro. There is electrophysiological evidence for a disordered excitation-contraction coupling in MG patients. The presence of titin antibodies, which bind to key regions near the A/I junction and in the central I-band, correlates with myopathy in MG patients. However, so far, there is no direct evidence that antibodies against the intracellular antigens RyR and titin are pathogenic in vivo.
Key Words: myasthenia gravis • acetylcholine receptor • ryanodine receptor • titin • antibodies
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