Immunolocalization of transcription factor NF-κB in inclusion-body myositis muscle and at normal human neuromuscular junctions

To investigate whether nuclear factor kappa B (NF-kappa B) is involved in the pathogenesis of inclusion-body myositis (IBM), we immunostained muscle biopsies of eight patients with IBM with specific antibodies against its p50 and p65 subunits. Approximately 70% of IBM vacuolated muscle fibers had strong focal accumulations of both NF-kappa B p50 and p65, which by immunoelectronmicroscopy, localized mainly to clusters of paired-helical filaments (PHFs). Virtually all necrotic fibers, in various muscle biopsies, had diffusely strong p50 immunoreactivity, whereas p65 immunoreactivity was present only in a small subset of necrotic fibers. At all neuromuscular junctions, postsynaptically there was strong p65 but no p50 immunoreactivity. Our data suggest that NF-kappa B plays a role in IBM pathogenesis. Different distributions of NF-kappa B subunits in necrotic fibers and at normal neuromuscular junctions (NMJs) suggests different roles of each subunit in human muscle pathology and physiology. (C) 1998 Elsevier Science Ireland Ltd. Ail rights reserved.