title: Nuclear membrane proteins are present within rimmed vacuoles in inclusion-body myositis.
abstract: The rimmed vacuoles within muscle in inclusion-body myositis (IBM) are structures of uncertain origin. Two hypotheses have been proposed for their formation: that they develop as a consequence of abnormal lysosomal function or in association with the breakdown of myonuclei. We tested the latter hypothesis by studying muscle samples from 14 patients with IBM and 18 controls using immunohistochemistry for nuclear membrane proteins, examining semithin sections, and performing electron microscopy. We found that in IBM muscle vacuoles were immunoreactive for the inner nuclear membrane proteins emerin and lamin A/C. Myonuclei with fragmented or focally absent nuclear membranes were present in immunohistochemical and electron microscopy studies. The association of nuclear membrane proteins with rimmed vacuoles confirms the hypotheses that rimmed vacuoles in IBM form in association with myonuclear pathology and that IBM differs from other inflammatory myopathies in that abnormalities of myonuclei are more prominent.
authors.affiliation: Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. sagreenberg@partners.org
authors.forename: Steven A
authors.initials: SA
authors.lastname: Greenberg
authors.forename: Jack L
authors.initials: JL
authors.lastname: Pinkus
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Amato
mesh_terms: D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D018979:Myositis, Inclusion Body / Q000378:metabolism* / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure
chemical_list: D016189:Dystrophin; C494847:LMNA protein, human; D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; C092710:emerin