Pathogenesis of ANCA-associated vasculitis: new possibilities for intervention.

Abstract

The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) comprise granulomatosis with polyangiitis (GPA), primarily associated with antibodies to proteinase 3 (PR3-ANCA); microscopic polyangiitis (MPA); and eosinophilic granulomatosis with polyangiitis (EGPA), both principally associated with antibodies to myeloperoxidase (MPO-ANCA). Genetic and environmental factors are involved in their etiopathogenesis, with a possible role for silica exposure in AAVs and Staphylococcus aureus infection in GPA. The distinct associations of PR3-ANCA and MPO-ANCA with different HLA class II antigens, which are stronger than those with the associated diseases, suggest a pathogenic role for those ANCAs and indicate that GPA and MPA are different diseases. Both in vitro and in vivo experimental data have shown that MPO-ANCA can induce necrotizing small-vessel vasculitis and glomerulonephritis. The additional role of the alternative pathway of complement activation has been demonstrated in human and experimental pathology. Also, T cells seem to be involved in lesion development, particularly in the kidney. Granuloma formation, as seen in PR3-ANCA-associated GPA, is not well explained by the presence of autoantibodies in experimental models. Here, T cells seem crucial. Recently obtained insights into the pathogenesis of AAVs have led to more targeted treatment of these life-threatening diseases.

• Authors: Cees G M Kallenberg, Coen A Stegeman, Wayel H Abdulahad, Peter Heeringa
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 62 Issue 6 Pg. 1176-87 (Dec 2013) ISSN: 1523-6838 [Electronic] United States
• PMID: 23810690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Histocompatibility Antigens Class II
• Silicon Dioxide
• Peroxidase
• Myeloblastin

Topics

• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (genetics, immunology)
• Churg-Strauss Syndrome (genetics, immunology)
• Complement Pathway, Alternative (genetics, immunology)
• Gene-Environment Interaction
• Genetic Predisposition to Disease (genetics)
• Glomerulonephritis (genetics, immunology)
• Histocompatibility Antigens Class II (genetics)
• Humans
• Microscopic Polyangiitis (genetics, immunology)
• Myeloblastin (immunology)
• Peroxidase (genetics, immunology)
• Polyarteritis Nodosa (genetics, immunology)
• Silicon Dioxide (adverse effects)
• Staphylococcal Infections (complications, genetics)
• T-Lymphocytes (immunology)