Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis
PloS one(2023)
Abstract
Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis typically associated with release of neutrophil extracellular traps (NETs) by activated neutrophils. In this study, we further aimed to investigate the contributions of neutrophils and NETs to the complex disease pathogenesis. We characterized the phenotype of neutrophils and their capacity to induce NETs. In addition, the level of circulating NETs, determined by neutrophil elastase/DNA complexes, and the capacity of patient sera to degrade NETs were investigated from blood samples of 12 GPA patients, 21 patients with systemic lupus erythematosus (SLE) and 21 healthy donors (HD). We found that GPA patients had significantly increased levels of low-density granulocytes (LDGs) compared to HD, which displayed an activated and more immature phenotype. While the propensity of normal-density granulocytes to release NETs and the levels of circulating NETs were not significantly different from HD, patient sera from GPA patients degraded NETs less effectively, which weakly correlated with markers of disease activity. In conclusion, increased levels of immature and activated LDGs and altered degradation of circulating NETs may contribute to pathogenesis of GPA, potentially by providing a source of autoantigens that trigger or further enhance autoimmune responses.
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Key words
neutrophil extracellular traps,granulomatosis,low density granulocytes
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