Progressive myopathy with up-regulation of MHC-I associated with statin therapy
Progressive myopathy with up-regulation of MHC-I associated with statin therapy
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DOI：
10.1016/j.nmd.2006.10.007
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发表时间：
2007-02-01
影响因子：
2.8
通讯作者：
Mastaglia, Frank L.
中科院分区：
文献类型：
--
作者：
Needham, Merrilee;Fabian, Victoria;Mastaglia, Frank L.
他汀类药物可引起坏死性肌病和高血糖血症，停药后这种情况是可逆的。不太为人所知的是一种现象，即他汀类药物可能会引发肌病，在停药后仍会持续或可能会恶化。我们对8例此类病例的肌肉病理进行了观察。所有患者均有肌纤维坏死，但仅有3例有炎性浸润性改变。在所有病例中，即使在非坏死性纤维中，MHC-I的表达也有弥漫性或多灶性上调。7例在强的松龙和甲氨蝶呤开始治疗后逐渐改善，1例自发改善。这些观察表明，他汀类药物可能引发一种免疫介导的肌病，在停药后持续存在，并对免疫抑制治疗有反应。这种肌病的机制尚不清楚，但可能涉及他汀类药物诱导的内质网应激反应，以及相关的MHC-I表达上调和肌肉纤维的抗原提呈。(C)2007年，爱思唯尔出版。
Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres. (C) 2007 Published by Elsevier B.V.