title: New insight into the pathogenesis of vasculitis associated with antineutrophil cytoplasmic autoantibodies.
abstract: OBJECTIVE
  To review the clinical, in-vitro and experimental animal model evidence for the pathogenicity of antineutrophil cytoplasmic autoantibodies.
  
  
  RESULTS
  Recent reports on the value of plasma exchange in the treatment of severe antineutrophil cytoplasmic autoantibody-associated glomerulonephritis support the importance of circulating antibodies. The correlation of antineutrophil cytoplasmic autoantibody positivity with renal disease in Churg-Strauss syndrome suggests that the vasculitic component of this syndrome may be induced by antineutrophil cytoplasmic autoantibodys but that other components have a different pathogenesis. In-vitro studies indicate that myeloperoxidase antineutrophil cytoplasmic autoantibody immunoglobulin G may be involved in pathogenesis not only by activating neutrophils but also by having pathophysiologic effects on the function of myeloperoxidase molecules. Findings using the mouse model of antineutrophil cytoplasmic autoantibody disease that is induced by intravenous injection of anti-myeloperoxidase indicate an unexpected role for the alternative pathway of complement activation in the pathogenesis of antineutrophil cytoplasmic autoantibody disease. This is substantiated by in-vitro observations showing that human myeloperoxidase antineutrophil cytoplasmic autoantibody immunoglobulin G and proteinase 3 antineutrophil cytoplasmic autoantibody immunoglobulin G cause neutrophils to release factors that activate complement.
  
  
  CONCLUSIONS
  Clinical, in-vitro and experimental animal model evidence continues to mount in favor of a pathogenic role of antineutrophil cytoplasmic autoantibody immunoglobulin G in the induction of vasculitis and glomerulonephritis. This emerging understanding of the pathogenic process may reveal novel and more effective approaches to treatment.
authors.affiliation: School of Medicine, University of North Carolina at Chapel Hill, North Carolina 27599-7525, USA. jcj@med.unc.edu
authors.forename: J Charles
authors.initials: JC
authors.lastname: Jennette
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Falk
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D053146:Myeloblastin / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D014657:Vasculitis / Q000276:immunology* / Q000503:physiopathology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D009195:Peroxidase; D053146:Myeloblastin