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  • Review Article
  • Published:

ANCA-associated vasculitides—advances in pathogenesis and treatment

Nature Reviews Rheumatology volume 6, pages 653–664 (2010)Cite this article

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Abstract

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) include Wegener granulomatosis, microscopic polyangiitis, Churg–Strauss syndrome and renal-limited vasculitis. This Review highlights the progress that has been made in our understanding of AAV pathogenesis and discusses new developments in the treatment of these diseases. Evidence from clinical studies, and both in vitro and in vivo experiments, supports a pathogenic role for ANCAs in the development of AAV; evidence is stronger for myeloperoxidase-ANCAs than for proteinase-3-ANCAs. Neutrophils, complement and effector T cells are also involved in AAV pathogenesis. With respect to treatment of AAV, glucocorticoids, cyclophosphamide and other conventional therapies are commonly used to induce remission in generalized disease. Pulse intravenous cyclophosphamide is equivalent in efficacy to oral cyclophosphamide but seems to be associated with less adverse effects. Nevertheless, alternatives to cyclophosphamide therapy have been investigated, such as the use of methotrexate as a less-toxic alternative to cyclophosphamide to induce remission in non-organ-threatening or non-life-threatening AAV. Furthermore, rituximab is equally as effective as cyclophosphamide for induction of remission in AAV and might become the standard of therapy in the near future. Controlled trials in which specific immune effector cells and molecules are being therapeutically targeted have been initiated or are currently being planned.

Key Points

  • Antineutrophil cytoplasmic antibodies (ANCAs), neutrophils and complement are the three main active participants in the pathogenesis of ANCA-associated vasculitides (AAV)

  • In addition, T cells are effector cells in AAV, particularly in proteinase-3-ANCA-associated Wegener granulomatosis

  • Glucocorticoids, in combination with cyclophosphamide, are the mainstay of therapy in generalized AAV, but rituximab is equally as effective as cyclophosphamide for induction of remission

  • For induction of remission, methotrexate can replace cyclophosphamide for early AAV; pulse cyclophosphamide is as effective as the daily oral cyclophosphamide regimen and causes fewer adverse effects

  • Both azathioprine and methotrexate are effective for maintenance therapy and are associated with less toxic effects than cyclophosphamide

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Figure 1: Classification algorithm for AAV.2
Figure 2: Etiologic and pathogenic factors in AAV.
Figure 3: The alternative complement pathway in AAV pathogenesis.
Figure 4: Pathogenic immune mechanisms in AAV.

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Acknowledgements

Charles. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. Renal Division, Peking University First Hospital, Beijing, 100034, China

    Min Chen

  2. Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands

    Cees G. M. Kallenberg

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M. Chen and C. G. M. Kallenberg contributed equally to researching data for the article, discussion of the content, writing the article and review and editing of the manuscript before submission.

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Correspondence to Cees G. M. Kallenberg.

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C. G. M. Kallenberg receives grant/research support from Genentech and ITN-NIH. M. Chen declares no competing interests.

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Chen, M., Kallenberg, C. ANCA-associated vasculitides—advances in pathogenesis and treatment. Nat Rev Rheumatol 6, 653–664 (2010). https://doi.org/10.1038/nrrheum.2010.158

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