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.

journal_name

Autoimmun Rev

journal_title

Autoimmunity reviews

authors

Creus KK,De Paepe B,De Bleecker JL

doi

10.1016/j.autrev.2009.02.026

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

627-31

issue

7

eissn

1568-9972

issn

1873-0183

pii

S1568-9972(09)00043-3

journal_volume

8

pub_type

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