The pathogenic role of antineutrophil cytoplasmic autoantibodies.

Antineutrophil cytoplasmic autoantibodies (ANCA) are found in the sera of patients with systemic necrotizing vasculitis and glomerulonephritis. Their role in the pathogenesis of these diseases is not clearly understood; however, there is a growing body of data that supports a pathogenic function for these antibodies. In vitro they can activate neutrophils and monocytes to produce reactive oxygen species (ROS), degranulate, and damage target cells. The antigens to which they are directed stimulate T lymphocytes from patients with these diseases. The ANCA directed against proteinase 3 (PR3) may also play a role in growth regulation of monocytes by inactivating the enzymatic function of its antigen. The proposed model of ANCA-induced disease takes into account both the in vitro data and the natural history of these diseases.