Small-vessel vasculitis (SVV) is a chronic autoimmune disease linked to antineutrophil cytoplasmic autoantibodies (ANCAs). This study shows that ANCAs stimulate neutrophils to release neutrophil extracellular traps (NETs), which contain autoantigens like proteinase-3 (PR3) and myeloperoxidase (MPO). These NETs contribute to vasculitis and autoimmune responses in SVV patients. ANCAs target granule proteins in neutrophils, such as PR3 and MPO, and activate neutrophils, leading to NET formation. NETs are formed through a unique type of cell death involving the release of chromatin fibers. These NETs can trap microbes and cause tissue damage, similar to neutrophil-induced inflammation in SVV. ANCAs activate the respiratory burst in neutrophils, leading to NET formation. The study found that ANCA-IgG induced NET formation in neutrophils, with 23% of cells producing NETs compared to 11% in control groups. PMA, a known NET inducer, triggered NET formation in 38% of neutrophils. NETs contain PR3 and MPO, which are autoantigens. Immunofluorescence analysis confirmed that PR3 and MPO localize with extracellular chromatin fibers. Additionally, LL37, a neutrophil-derived antimicrobial peptide, was found on NETs, which may activate plasmacytoid dendritic cells (pDCs) and contribute to autoimmune responses. In vivo, NETs were detected in kidney biopsies of SVV patients, with NETs containing PR3 and MPO. These NETs were decorated with LL37 and were associated with increased IFN-α production, indicating pDC activation. Circulating MPO-DNA complexes were found in SVV patients, suggesting NET formation. These findings indicate that NETs play a role in the pathogenesis of SVV, contributing to autoimmune responses and tissue damage. The study highlights the importance of NET formation in SVV and suggests that targeting NET formation could be a therapeutic approach.Small-vessel vasculitis (SVV) is a chronic autoimmune disease linked to antineutrophil cytoplasmic autoantibodies (ANCAs). This study shows that ANCAs stimulate neutrophils to release neutrophil extracellular traps (NETs), which contain autoantigens like proteinase-3 (PR3) and myeloperoxidase (MPO). These NETs contribute to vasculitis and autoimmune responses in SVV patients. ANCAs target granule proteins in neutrophils, such as PR3 and MPO, and activate neutrophils, leading to NET formation. NETs are formed through a unique type of cell death involving the release of chromatin fibers. These NETs can trap microbes and cause tissue damage, similar to neutrophil-induced inflammation in SVV. ANCAs activate the respiratory burst in neutrophils, leading to NET formation. The study found that ANCA-IgG induced NET formation in neutrophils, with 23% of cells producing NETs compared to 11% in control groups. PMA, a known NET inducer, triggered NET formation in 38% of neutrophils. NETs contain PR3 and MPO, which are autoantigens. Immunofluorescence analysis confirmed that PR3 and MPO localize with extracellular chromatin fibers. Additionally, LL37, a neutrophil-derived antimicrobial peptide, was found on NETs, which may activate plasmacytoid dendritic cells (pDCs) and contribute to autoimmune responses. In vivo, NETs were detected in kidney biopsies of SVV patients, with NETs containing PR3 and MPO. These NETs were decorated with LL37 and were associated with increased IFN-α production, indicating pDC activation. Circulating MPO-DNA complexes were found in SVV patients, suggesting NET formation. These findings indicate that NETs play a role in the pathogenesis of SVV, contributing to autoimmune responses and tissue damage. The study highlights the importance of NET formation in SVV and suggests that targeting NET formation could be a therapeutic approach.