Sarcoplasmic redistribution of nuclear TDP‐43 in inclusion body myositis |
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| Authors: | Mohammad Salajegheh MD Jack L. Pinkus PhD J.Paul Taylor MD PhD Anthony A. Amato MD Remedios Nazareno BS Robert H. Baloh MD PhD Steven A. Greenberg MD |
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| Affiliation: | 1. Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA;2. Children's Hospital Informatics Program, Children's Hospital Boston, Massachusetts, USA;3. Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA;4. Department of Neurology, Neuromuscular Division, Washington University School of Medicine, St. Louis, Missouri, USA |
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| Abstract: | 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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| Keywords: | inclusion body myositis inflammatory myopathies TDP‐43 |
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