Sarcoplasmic redistribution of nuclear TDP-43 in inclusion body myositis.
Mohammad Salajegheh, Jack L Pinkus, J Paul Taylor, Anthony A Amato, Remedios Nazareno, Robert H Baloh, Steven A Greenberg
Author Information
Mohammad Salajegheh: Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA. msalajegheh@partners.org
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-43sarcoplasmic 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 sarcoplasmicTDP-43 was highly sensitive (91%) and specific (100%) to IBM among 50 inflammatory myopathypatient samples, although some patients with hereditary inclusion body myopathies and myofibrillar myopathy also had sarcoplasmicTDP-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.
