Skeie G O, Aarli J A, Gilhus N E
Department of Clinical Medicine, University of Bergen and Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Acta Neurol Scand Suppl. 2006;183:19-23. doi: 10.1111/j.1600-0404.2006.00608.x.
Some myasthenia gravis (MG) patients have antibodies against skeletal muscle antigens in addition to the acetylcholine receptor (AChR). Two major antigens for non-AchR antibodies in MG are the Ca(2+) 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 mainly in thymoma MG patients and in a few late-onset MG patients and correlate with a severe MG disease. The presence of titin antibodies, which bind to key regions near the A/I junction and in the central I-band, correlates with myopathy. The immunosuppressant (FK506), which enhances Ca(2+) release from the RyR, seems to have a symptomatic effect on MG patients with RyR antibodies. The RyR antibodies recognize a region near the N-terminus important for channel regulation and inhibit Ca(2+) release in vitro. However, evidence that antibodies against the intracellular antigens RyR and titin are pathogenic in vivo is still missing.
一些重症肌无力（MG）患者除了有抗乙酰胆碱受体（AChR）抗体外，还存在抗骨骼肌抗原的抗体。MG中抗非AChR抗体的两个主要抗原是肌浆网的Ca(2+)释放通道、兰尼碱受体（RyR）和肌联蛋白，肌联蛋白是一种对肌肉结构、功能和发育至关重要的巨大丝状肌肉蛋白。RyR和肌联蛋白抗体主要在胸腺瘤MG患者和少数晚发型MG患者中发现，并与严重的MG疾病相关。与A/I交界处附近和中央I带中的关键区域结合的肌联蛋白抗体的存在与肌病相关。增强RyR释放Ca(2+)的免疫抑制剂（FK506）似乎对有RyR抗体的MG患者有对症作用。RyR抗体识别对通道调节很重要的N端附近区域，并在体外抑制Ca(2+)释放。然而，针对细胞内抗原RyR和肌联蛋白的抗体在体内具有致病性的证据仍然缺失。
