Pathophysiology of ANCA-associated small vessel vasculitis

Curr Rheumatol Rep. 2010 Dec;12(6):399-405. doi: 10.1007/s11926-010-0138-6.

Abstract

Antineutrophil cytoplasmic autoantibodies (ANCAs) directed to proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are strongly associated with the ANCA-associated vasculitides--Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical observations, including the efficacy of B-cell depletion via rituximab treatment, support--but do not prove--a pathogenic role for ANCA in the ANCA-associated vasculitides. In vitro experimental studies show that the interplay of ANCA, neutrophils, the alternative pathway of the complement system, and endothelial cells could result in lysis of the endothelium. A pathogenic role for MPO-ANCA is strongly supported by in vivo experimental studies in mice and rats, which also elucidate the pathogenic mechanisms involved in lesion development. Unfortunately, an animal model for PR3-ANCA-associated Wegener's granulomatosis is not yet available. Here, cellular immunity appears to play a major role as well, particularly via interleukin-17-producing T cells, in line with granulomatous inflammation in the lesions. Finally, microbial factors, in particular Staphylococcus aureus and gram-negative bacteria, seem to be involved in disease induction and expression, but further studies are needed to define their precise role in disease development.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Antineutrophil Cytoplasmic / blood*
  • Cells, Cultured
  • Disease Models, Animal
  • Humans
  • Immunity, Cellular / immunology
  • Mice
  • Microscopic Polyangiitis / immunology
  • Microscopic Polyangiitis / pathology
  • Microscopic Polyangiitis / physiopathology*
  • Myeloblastin / immunology
  • Neutrophils / cytology
  • Neutrophils / immunology
  • Peroxidase / immunology
  • Rats
  • Staphylococcus aureus / immunology
  • Staphylococcus aureus / pathogenicity
  • Th17 Cells / immunology

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Peroxidase
  • Myeloblastin