This study investigates the role of neutrophil extracellular traps (NETs) in small-vessel vasculitis (SVV), an autoinflammatory condition linked to antineutrophil cytoplasm autoantibodies (ANCAs). The authors found that ANCA-stimulated neutrophils release chromatin fibers (NETs) containing targeted autoantigens proteinase-3 (PR3) and myeloperoxidase (MPO). In vitro experiments showed that ANCA-IgG primed neutrophils produced robust NETs, with 23% of neutrophils producing NETs compared to 11% with control IgG. In vivo analysis of kidney biopsies from individuals with SVV revealed NETs containing autoantigens and immunostimulatory peptides, suggesting that NET formation is a key mechanism in the disease. Additionally, the study found increased expression of interferon-α (IFN-α) and circulating MPO-DNA complexes in serum samples from individuals with active SVV, further supporting the role of NETs in the autoimmune response. The findings suggest that NETs may perpetuate a vicious cycle of antigen-chromatin complex delivery to the immune system, contributing to the chronicity of SVV.This study investigates the role of neutrophil extracellular traps (NETs) in small-vessel vasculitis (SVV), an autoinflammatory condition linked to antineutrophil cytoplasm autoantibodies (ANCAs). The authors found that ANCA-stimulated neutrophils release chromatin fibers (NETs) containing targeted autoantigens proteinase-3 (PR3) and myeloperoxidase (MPO). In vitro experiments showed that ANCA-IgG primed neutrophils produced robust NETs, with 23% of neutrophils producing NETs compared to 11% with control IgG. In vivo analysis of kidney biopsies from individuals with SVV revealed NETs containing autoantigens and immunostimulatory peptides, suggesting that NET formation is a key mechanism in the disease. Additionally, the study found increased expression of interferon-α (IFN-α) and circulating MPO-DNA complexes in serum samples from individuals with active SVV, further supporting the role of NETs in the autoimmune response. The findings suggest that NETs may perpetuate a vicious cycle of antigen-chromatin complex delivery to the immune system, contributing to the chronicity of SVV.