Pathogenesis of ANCA-associated systemic vasculitis

J Pathol. 2000 Feb;190(3):349-59. doi: 10.1002/(SICI)1096-9896(200002)190:3<349::AID-PATH524>3.0.CO;2-A.

Abstract

The aetiology of primary systemic vasculitides remains unknown. Recent advances have been made in the understanding of relevant mechanisms of inflammation, particularly the role of the endothelium and interactions with inflammatory mediators and immune effector cells. In Wegener's granulomatosis and microscopic polyangiitis the evidence suggests an autoimmune inflammatory process, characterized by an early lesion involving neutrophils and endothelial cells as both targets and active participants; priming of neutrophils and endothelial cells allows ANCA to activate neutrophils with damage localized to the endothelium. In the absence of immune complex deposition, the role of the ANCA is particularly intriguing. Endothelial cell damage and activation produces pro-inflammatory mediators with influx monocytes and T cells intensifying damage. Increased understanding of the pathogenesis of systemic vasculitis is likely to provide the basis for the use of more selective immunomodulatory therapies in the future.

Publication types

  • Review

MeSH terms

  • Antibodies, Antineutrophil Cytoplasmic / physiology*
  • Churg-Strauss Syndrome / etiology*
  • Churg-Strauss Syndrome / genetics
  • Churg-Strauss Syndrome / physiopathology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiopathology
  • Granulomatosis with Polyangiitis / etiology*
  • Granulomatosis with Polyangiitis / genetics
  • Granulomatosis with Polyangiitis / physiopathology
  • Humans
  • Immunity, Cellular
  • Inflammation Mediators / physiology
  • Monocytes / physiology
  • Neutrophil Infiltration / physiology
  • Neutrophils / physiology
  • T-Lymphocytes / physiology

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Inflammation Mediators