Antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis.

Objective: This review focuses on recent advances in the diagnosis, pathogenesis and treatment of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis.

Results: Antineutrophil cytoplasmic autoantibodies are closely associated with Wegener's granulomatosis and microscopic polyangiitis. Within the Churg-Strauss syndrome, antineutrophil cytoplasmic autoantibodies, mostly directed towards myeloperoxidase, characterize patients with glomerulonephritis and small-vessel vasculitis. There is increasing evidence that myeloperoxidase-antineutrophil cytoplasmic autoantibodies are directly involved in the pathogenesis of necrotizing vasculitis. This is less clear for proteinase 3-antineutrophil cytoplasmic autoantibodies, markers for Wegener's granulomatosis. With respect to proteinase 3-antineutrophil cytoplasmic autoantibodies, complementary proteinase 3, a peptide translated from the antisense DNA strand of proteinase 3 and homologous to several microbial peptides, may be involved in induction of proteinase 3-antineutrophil cytoplasmic autoantibodies. Currently, various controlled trials have been initiated. Methotrexate has been shown to be effective for induction of remission in locoregional Wegener's granulomatosis. Other trials are underway.

Conclusions: Apart from its diagnostic potential, antineutrophil cytoplasmic autoantibodies, particularly myeloperoxidase-antineutrophil cytoplasmic autoantibodies, are directly involved in the pathogenesis of the associated vasculitides. New treatment modalities, supposedly more efficacious and less toxic than daily oral cyclophosphamide, are being tested in randomized controlled trials.