Is Wegener's granulomatosis an autoimmune disease?

Wegener's granulomatosis is a multisystem disease characterized by granulom ata of the respiratory tract and systemic necrotising vasculitis. There is a strong and specific association with autoantibodies directed against prot einase 3, a constituent of neutrophril azurophilic granules. Antibody titer s correlate with clinical disease activity and predict relapses. The diseas e responds favorably to immunosuppressive therapy. The pathogenicity of ant ineutrophil cytoplasmic antibodies (ANCA), however, remains unproven. in vi tro, the expression of proteinase-3 and other ANCA antigens on the surface of neutrophils and monocytes can be induced by priming with proinflammatory cytokines. Antineutrophil cytoplasmic antibodies are then able to activate these leukocytes, stimulating degranulation, the production of reactive ox ygen species, and the secretion of further cytokines. Neutrophils activated by ANCA, and possibly ANCA alone, directly damage endothelial cells in vit ro, An animal model of proteinase 3-ANCA-induced vasculitis has not been fo und. Antineutrophil cytoplasmic antibodies directed against another antigen , myeloperoxidase, are not sufficient to cause vasculitis but they promote damage in certain animal models. Thus, a considerable amount of evidence su pports the notion that Wegener's granulomatosis is an autoimmune disease. ( C) 2000 Lippincott Williams & Wilkins, Inc.