Anti-aminoacyl tRNA synthetase immune responses: Insights into the pathogenesis of the idiopathic inflammatory myopathies

Research output: Contribution to journalReview articlepeer-review

Abstract

Purpose of review: One of the most striking humoral characteristics of the idiopathic inflammatory myopathies is the specific targeting of components of the translational machinery by the immune system. The most commonly targeted of these components are the aminoacyl tRNA synthetase (ARS) molecules. However, the relation between the immune responses to these molecules and the pathogenesis of the inflammatory myopathies remains obscure. This review will examine recent evidence that explores the links between the ARS molecules, inflammation, and apoptosis, with the aim of furthering our current understanding of the underlying pathogenesis of the myositis syndromes. Recent findings: Several of the ARS molecules and their proteolytic fragments generated during inflammation and apoptosis have recently been shown to possess chemoattractant properties. The liberation of these fragments in the muscle microenvironment under certain circumstances may provide a proinflammatory context and lead to the influx of lymphocytes, macrophages, and specialized antigen-presenting cells to the site of muscle injury. The subsequent processing and presentation of these autoantigen fragments on major histocompatibility complex class I and II molecules may generate an ARS-specific autoimmune response, which may be responsible for amplification and propagation of muscle injury in these diseases. Summary: The striking association between the inflammatory myopathies and anti-ARS antibodies implies a role for the ARS molecules in the pathogenesis of these syndromes. Recent data suggest that ARS molecules and their proteolytic fragments generated during the cell death process may be responsible for priming and sustaining a specific immune response in situ in myositis. How these molecules become altered and access the immune system in the disease microenvironment is an area of ongoing investigation.

Original languageEnglish (US)
Pages (from-to)708-713
Number of pages6
JournalCurrent opinion in rheumatology
Volume15
Issue number6
DOIs
StatePublished - Nov 2003

Keywords

  • Aminoacyl tRNA synthetase
  • Autoantibodies
  • Granzyme B
  • Myositis

ASJC Scopus subject areas

  • Rheumatology

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