Early disintegration of myonuclear fibrous lamina in inclusion body myositis: Ultrastructural and immunohistochemical studies

Objective Morphological analyses to assess the integrity of myonuclear surface structures in muscle biopsies from patients with inclusion body myositis (IBM) and related disorders were carried out to find clues to the causes of IBM. Methods Muscle biopsies from 26 patients (seven with IBM, five polymyositis, three dermatomyositis, one hereditary inclusion body myopathy associated with Paget disease and front-temporal dementia, three with other non-inflammatory myopathies, four with no pathological abnormalities and three type 2 fiber atrophy only) were assessed by measuring lengths of clearly identifiable muscle outer (ONM) and inner nuclear membranes (INM), and fibrous laminae (FL) on electron micrographs, and grading severity of degenerative changes in the sarcoplasm into three stages. The nuclei of capillary endothelial cells were also examined and lamin A/C, a major constituent of FL, localized immunohistochemically. Results Compared with patients with no pathology or type 2 fiber atrophy only, polymyositis had significantly less ONM, INM and FL at an advanced stage of degeneration. In dermatomyositis, ONM was moderately decreased. In IBM, ONM, INM and FL were decreased severely from early stages of muscle fiber degeneration. In the one case with inclusion body myopathy associated with Paget disease and front-temporal dementia, all three layers, particularly ONM, were decreased. No significant changes were observed in the nuclei of capillary endothelial cells in IBM or other conditions. In IBM, there was less lamin A/C in myonuclei than in capillary endothelial cell nuclei. Conclusions In IBM, shorter lengths of myonuclear surface structures, particularly of FL, were observed from an early stage of degeneration. Early disintegration of FL might reflect an essential pathomechanism of IBM.