SARCOPLASMIC REDISTRIBUTION OF NUCLEAR TDP-43 IN INCLUSION BODY MYOSITIS

被引:157
作者
Salajegheh, Mohammad [1 ,2 ,3 ]
Pinkus, Jack L. [1 ,2 ,3 ]
Taylor, J. Paul [4 ]
Amato, Anthony A. [1 ,2 ]
Nazareno, Remedios [1 ,2 ,3 ]
Baloh, Robert H. [5 ]
Greenberg, Steven A. [1 ,2 ,3 ]
机构
[1] Brigham & Womens Hosp, Dept Neurol, Div Neuromuscular Dis, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Childrens Hosp, Informat Program, Boston, MA 02115 USA
[4] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA
[5] Washington Univ, Sch Med, Dept Neurol, Neuromuscular Div, St Louis, MO 63110 USA
关键词
inclusion body myositis; inflammatory myopathies; TDP-43; BETA-AMYLOID PROTEIN; RIMMED VACUOLES; MUSCLE-FIBERS; CONGO-RED; LOCALIZATION; ACCUMULATION; POLYMYOSITIS; MYOPATHIES; EXPRESSION; EPITOPES;
D O I
10.1002/mus.21386
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The nucleic acid binding protein TDP-43 was recently identified in normal myonuclei and in the sarcoplasm of inclusion body myositis (IBM) muscle. Here we found TDP-43 sarcoplasmic immunoreactivity in 23% of IBM myofibers, while other reported IBM biomarkers were less frequent, with rimmed vacuoles in 2.8%, fluorescent Congo red material in 0.57%, SMI-31 immunoreactivity in 0.83%, and focal R1282 beta-amyloid immunoreactivity in 0.00% of myofibers. The presence of as little as >1% of myofibers with nonnuclear sarcoplasmic TDP-43 was highly sensitive (91%) and specific (100%) to IBM among 50 inflammatory myopathy patient samples, although some patients with hereditary inclusion body myopathies and myofibrillar myopathy also had sarcoplasmic TDP-43. TDP-43 mutations were sought, and none were identified. TDP-43 could be one of many nucleic acid binding proteins that are abnormally present in IBM sarcoplasm. They could potentially interfere with the normal function of extranuclear RNAs that maintain myofiber protein production. Muscle Nerve 40: 19-31, 2009
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页码:19 / 31
页数:13
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