1. Pathogenesis of ANCA-Associated Vasculitis: New Possibilities for Intervention
- Author
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Wayel H. Abdulahad, Peter Heeringa, Coen A. Stegeman, Cees G. M. Kallenberg, Groningen Kidney Center (GKC), and Translational Immunology Groningen (TRIGR)
- Subjects
Pathology ,Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis ,T-Lymphocytes ,Complement Pathway, Alternative ,Microscopic Polyangiitis ,ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES ,Churg-Strauss Syndrome ,T-CELL-ACTIVATION ,Glomerulonephritis ,immune system diseases ,Proteinase 3 ,Medicine ,skin and connective tissue diseases ,antibodies to proteinase 3 (PR3-ANCA) ,pathogenesis ,HUMAN NEUTROPHILS ,Staphylococcal Infections ,Silicon Dioxide ,POLYANGIITIS WEGENERS ,Nephrology ,Experimental pathology ,CRESCENTIC GLOMERULONEPHRITIS ,Microscopic polyangiitis ,Granulomatosis with polyangiitis ,Vasculitis ,INTERACTIONS IN-VIVO ,medicine.medical_specialty ,Myeloblastin ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,SMALL-VESSEL VASCULITIS ,WEGENERS-GRANULOMATOSIS ,Antigen ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,Peroxidase ,Anti-neutrophil cytoplasmic antibody ,PROTEINASE-3 PR3 ,business.industry ,microscopic polyangiitis (MPA) ,Histocompatibility Antigens Class II ,Autoantibody ,antibodies to myeloperoxidase (MPO-ANCA) ,medicine.disease ,ENDOTHELIAL-CELLS ,Polyarteritis Nodosa ,respiratory tract diseases ,Immunology ,Gene-Environment Interaction ,granulomatosis with polyangiitis (GPA) ,business - 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. (C) 2013 by the National Kidney Foundation, Inc.
- Published
- 2013
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