PMC9479327_01
Schematic diagram of the environmental factors in the onset of AAV. ANCA autoantigens (PR3 and MPO) are usually hidden in the primitive granules of neutrophils. Environmental factors such as silica, air pollution, and infection, lead to neutrophil initiation and PR3 and MPO movement to the cell surface. Binding of ANCA to these autoantigens leads to activation of neutrophils, which adhere to the vascular endothelium. Neutrophil degranulation leads to the release of reactive oxygen species (ROS), proteases and neutrophil extracellular traps (NETs), which in turn destroy endothelial cells. Chemokines and tissue deposition of PR3 and MPO lead to increased tissue damage by recruitment of autoreactive T cells and monocytes. Additionally, ANCA binds to cell surface autoantigens, leading to neutrophil activation and release of factors that activate the complement replacement pathway. The production of the allergenic toxin C5a further attracts neutrophils and enhances neutrophil initiation and activation upon binding to cell surface C5a receptors, thereby promoting vascular inflammation.
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AAV is unclear. A previous study found that silica does not have a direct toxic effect on genetically susceptible individuals but rather enhances the immune response non-specifically, activates T cells and Treg cells, and leads to autoimmune dysfunction ( Figure 1 ).