Pathogenesis of ANCA-Associated Vasculitis: New Possibilities for Intervention

Kallenberg, C. G. M., Stegeman, C. A., Abdulahad, W. H. & Heeringa, P., Dec-2013, In : American Journal of Kidney Diseases. 62, 6, p. 1176-1187 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1176-1187
Number of pages12
JournalAmerican Journal of Kidney Diseases
Issue number6
Publication statusPublished - Dec-2013


  • Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, antibodies to proteinase 3 (PR3-ANCA), antibodies to myeloperoxidase (MPO-ANCA), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), pathogenesis, ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES, SMALL-VESSEL VASCULITIS, INTERACTIONS IN-VIVO, T-CELL-ACTIVATION, WEGENERS-GRANULOMATOSIS, CRESCENTIC GLOMERULONEPHRITIS, POLYANGIITIS WEGENERS, ENDOTHELIAL-CELLS, HUMAN NEUTROPHILS, PROTEINASE-3 PR3

View graph of relations

ID: 5997369