Clinical Reviews in Allergy & Immunology

, Volume 41, Issue 2, pp 224–231

Pathogenesis of ANCA-Associated Vasculitis, an Update

Article

Abstract

Clinical observations, including a report of neonatal vasculitis occurring in a child born from a mother with anti-neutrophil cytoplasmic antibody directed to myeloperoxidase (MPO-ANCA)-associated vasculitis, suggest a pathogenic role for ANCA. Such a role is supported by in vitro experimental data showing that ANCA can activate primed neutrophils to the production of reactive oxygen species and lytic enzymes resulting in lysis of endothelial cells. An interplay between neutrophils, the alternative pathway of complement, and MPO-ANCA resulting in systemic vasculitis including necrotizing glomerulonephritis has clearly been demonstrated in animal models. An in vivo pathogenic role of ANCA directed to proteinase 3 (PR3-ANCA) has, however, not been substantiated. In PR3-ANCA-associated vasculitis, granulomatous inflammation points to involvement of cell-mediated immunity. In vitro studies, indeed, suggest that PR3-specific Th17 CD4-positive lymphocytes are operative in lesion development. The triggering role of microbial factors is becoming more clear. In particular Staphylococcus aureus carriage and infection with Gram-negative bacteria could contribute to induction and persistence of ANCA-associated vasculitis (AAV). Insight into the pathogenic pathways involved in AAV have opened and will further open new ways to targeted treatment.

Keywords

ANCA-associated vasculitis Pathogenesis PR3-ANCA MPO-ANCA Staphylococcus aureus 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Rheumatology and Clinical Immunology, AA21University Medical Center GroningenGroningenThe Netherlands

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