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ANCA-associated vasculitis: from bench research to novel treatments

Abstract

Small-vessel vasculitic syndromes such as Wegener granulomatosis and microscopic polyangiitis, which are associated with circulating antineutrophil cytoplasmic autoantibodies, are an important cause of renal failure. Current immunosuppressive regimens based on cyclophosphamide have significantly improved survival in patients with these conditions. However, such treatments are toxic, increase the risk of infection and do not cure the disease; fresh approaches are, therefore, required. An increased understanding of the pathogenesis of these syndromes has allowed the rational use of newer therapies such as rituximab, an anti-CD20 chimeric monoclonal antibody that depletes B cells. Further understanding of the disease pathogenesis is crucial to the development of novel targeted therapies, which are urgently required to improve patient prognosis. Future potential therapies include molecules that block signaling pathways that are essential in the pathogenesis of these diseases.

Key Points

  • Current treatment regimens for antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides that are based on cyclophosphamide have improved survival but are associated with significant morbidity

  • ANCAs are pathogenic antibodies that activate neutrophils and cause inflammation

  • B cells have a key role in the pathogenesis of ANCA-associated vasculitides and their removal using B-cell-depleting therapeutic antibodies offers hope for the future and is being investigated in randomized trials

  • Signaling pathways in neutrophils activated by ANCAs differ from those induced by immune complexes; molecules that block these pathways have shown benefit in animal models, providing hope for less-toxic therapies

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Figure 1: Renal biopsy findings in a patient with ANCA-associated vasculitis.
Figure 2: Pulmonary involvement in Wegener granulomatosis.
Figure 3: Immunofluorescence staining patterns of antineutrophil cytoplasmic antibodies (ANCAs).

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Correspondence to Lorraine Harper.

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Pallan, L., Savage, C. & Harper, L. ANCA-associated vasculitis: from bench research to novel treatments. Nat Rev Nephrol 5, 278–286 (2009). https://doi.org/10.1038/nrneph.2009.45

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