Wegener's granulomatosis--autoimmunity to neutrophil proteinase 3

Wegener's granulomatosis (WG) is a small-vessel vasculitis associated with various clinical manifestations, among which the most common are respiratory tract disease and glomerulonephritis leading to renal failure. The pathogenesis of vascular injury in WG is ascribed to antineutrophil cytoplasmic antibodies (ANCA) directed mainly against proteinase 3 (PR3), an enzyme from neutrophil granules. The reasons for the breakdown of self tolerance to PR3 are unknown, and together with the molecular mechanisms underlying this immunoinflammation, are the subject of research. Standard treatment of WG consists of cyclophosphamide and corticosteroids. In patients resistant to this therapy or with refractory disease, some alternative strategies involving tumor necrosis factor blockade, polyclonal antithymocyte globulin or monoclonal anti-T cell antibodies are applied.