Damage and inflammation in muscular dystrophy: potential implications and relationships with autoimmune myositis

Curr Opin Rheumatol. 2005 Nov;17(6):707-13. doi: 10.1097/01.bor.0000179948.65895.1a.

Abstract

Purpose of review: This review provides an updated evaluation of the role of inflammation in muscular dystrophy, and presents findings which suggest that non-immunological factors promote idiopathic inflammatory myopathies. Recent findings are summarized which indicate that immune-targeted interventions may provide useful approaches to treat muscular dystrophy.

Recent findings: Elevated expression of the cytotoxic T-lymphocyte derived cytolytic molecule, perforin, and the inducible costimulatory molecule have been identified in muscles of Duchenne muscular dystrophy patients, which strengthens evidence that a cellular immune response contributes to dystrophinopathy. Conversely, new findings implicate non-immune factors in inflammatory myopathy pathogenesis. Muscles from healthy individuals expressed autoantigens typically present in inflammatory myopathies, and autoantigen expression increased along with elevated major histocompatibility complex class I expression at sites of muscle regeneration in inflammatory myopathies. Those observations suggest that regeneration could render conditions sufficient for an autoimmune response in inflammatory myopathies. Further studies of corticosteroids or tumor necrosis factor blockade in treating dystrophinopathy indicate that immunological interventions may yield improved therapies for muscular dystrophy. In addition, advancements in understanding the involvement of chemokines in muscular dystrophy and inflammatory myopathies suggest that targeting specific chemokines has potential therapeutic value.

Summary: Our developing understanding of the pathogenesis of muscular dystrophies and inflammatory myopathies shows complex interactions between immunological and non-immunological features of these diseases that can affect disease onset and course. Among the muscular dystrophies, the best evidence for an immunological component to disease pathogenesis exists for dystrophinopathies. Conversely, muscle damage leading to regeneration may promote some inflammatory myopathies, although much remains to be learned concerning the identity and pathological significance of non-immunological features of inflammatory myopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Autoantigens / immunology
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Chemokines / immunology
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Muscular Dystrophies / drug therapy
  • Muscular Dystrophies / immunology*
  • Muscular Dystrophies / pathology
  • Myositis / immunology*
  • Myositis / pathology
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Autoantigens
  • Chemokines
  • Glucocorticoids
  • Immunosuppressive Agents