title: Idiopathic inflammatory myopathies and the classical NF-kappaB complex: current insights and implications for therapy.
abstract: The idiopathic inflammatory myopathies (IIM) comprise a heterogeneous group of muscle diseases. The three best-studied subgroups are dermatomyositis (DM), polymyositis (PM) and sporadic inclusion body myositis (IBM). The latter represents a steroid-refractory condition. PM and IBM are characterized by a cell-mediated immune response directed against non-necrotic fibers expressing Major Histocompatibility Complex class I (MHC class I). IBM presents with additional degenerative features, including rimmed vacuoles and depositions of aberrant proteins. DM is a complement-mediated endotheliopathy often accompanied by characteristic skin manifestations. The ubiquitously expressed transcription factor NF-kappaB is considered essential for the development of auto-immunity. This review describes data gathered so far concerning the distribution of the classical heterodimer p65/p50 and its inhibitor I-kappaBalpha in IIM skeletal muscle. Data suggest that the NF-kappaB complex plays a role in the endotheliopathy characterizing DM and might be involved in myofiber regeneration, and appoint CD4+ and CD68+ mononuclear cells with a more prominent role than previously assumed. Fragmentary knowledge of the immunopathogenesis of IIM hampers the development of therapeutic strategies suited to all patient groups. Unravelling the precise involvement of NF-kappaB subunits in IIM immunopathogenesis can shed new light onto the etiology of these diseases and may offer a novel therapeutic target.
authors.affiliation: Department of Neurology, Ghent University Hospital, Belgium.
authors.forename: Kim K
authors.initials: KK
authors.lastname: Creus
authors.forename: Boel
authors.initials: B
authors.lastname: De Paepe
authors.forename: Jan L
authors.initials: JL
authors.lastname: De Bleecker
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D046912:Multiprotein Complexes / Q000276:immunology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism; D009220:Myositis / Q000188:drug therapy / Q000276:immunology*; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015704:CD4 Antigens; D020672:I-kappa B Proteins; D046912:Multiprotein Complexes; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; C067980:CD68 antigen, human; D000097382:CD68 Molecule