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Pathophysiology of ANCA-associated small vessel vasculitis.

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.
AuthorsCees G M Kallenberg
JournalCurrent rheumatology reports (Curr Rheumatol Rep) Vol. 12 Issue 6 Pg. 399-405 (Dec 2010) ISSN: 1534-6307 [Electronic] United States
PMID20878509 (Publication Type: Journal Article, Review)
Chemical References
  • Antibodies, Antineutrophil Cytoplasmic
  • Peroxidase
  • Myeloblastin
Topics
  • Animals
  • Antibodies, Antineutrophil Cytoplasmic (blood)
  • Cells, Cultured
  • Disease Models, Animal
  • Humans
  • Immunity, Cellular (immunology)
  • Mice
  • Microscopic Polyangiitis (immunology, pathology, physiopathology)
  • Myeloblastin (immunology)
  • Neutrophils (cytology, immunology)
  • Peroxidase (immunology)
  • Rats
  • Staphylococcus aureus (immunology, pathogenicity)
  • Th17 Cells (immunology)

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