Pathogenic mechanisms of disease in myositis: autoantigens as clues

Curr Opin Rheumatol. 2009 Nov;21(6):604-9. doi: 10.1097/BOR.0b013e328331638a.

Abstract

Purpose of review: There is increasing evidence of autoimmunity in dermatomyositis and polymyositis, with strong correlations between particular myositis-specific autoantibodies (MSAs) and clinical subsets. It is now clear that corresponding autoantigens are selectively targeted, have distinct adjuvant properties and are upregulated in target tissues, suggesting a role in disease pathogenesis. This review highlights recent findings including the identification of novel MSAs and studies investigating autoantigen properties and expression in both target tissues and tumours.

Recent findings: During the review period, the clinical associations of anti-SAE and anti-p140 have been further described. Studies of autoantigen expression have demonstrated upregulation of Mi-2 in response to ultraviolet (UV) damage and expression of myositis-specific autoantigens in rat newborn skeletal muscle. The role of type I interferon and adjuvant activity has also been highlighted through the identification of the CADM140 autoantigen as MDA5, a protein involved in innate immunity.

Summary: There are now a number of models indicating roles of autoantigens in disease pathogenesis. Our increased understanding of the autoantigenic properties of these targeted proteins will help to determine the mechanisms involved in the initiation and propagation of myositis. In turn, these findings may lead to therapeutic advances including the development of more targeted treatments.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantibodies / metabolism
  • Autoantigens / metabolism*
  • Humans
  • Myositis / complications
  • Myositis / etiology*
  • Myositis / immunology*
  • Neoplasms / etiology
  • Neoplasms / immunology
  • Nervous System Autoimmune Disease, Experimental / etiology
  • Nervous System Autoimmune Disease, Experimental / immunology
  • Protein Processing, Post-Translational
  • Rats
  • Risk Factors
  • Toll-Like Receptors / metabolism

Substances

  • Autoantibodies
  • Autoantigens
  • Toll-Like Receptors