Neutrophil extracellular trap formation in anti-neutrophil cytoplasmic antibody-associated and large-vessel vasculitis.

Levels of neutrophil extracellular traps (NETs) were measured in plasma of healthy controls (HC, n = 30) and patients with granulomatosis with polyangiitis (GPA, n = 123), microscopic polyangiitis (MPA, n = 61), Takayasu's arteritis (TAK, n = 58), and giant cell arteritis (GCA, n = 68), at times of remission or activity and correlated with levels of the platelet-derived thrombospondin-1 (TSP-1). Levels of NETs were elevated during active disease in patients with GPA (p < 0.0001), MPA (p = 0.0038), TAK (p < 0.0001), and GCA (p < 0.0001), and in remission for GPA, p < 0.0001, MPA, p = 0.005, TAK, p = 0.03, and GCA, p = 0.0009. All cohorts demonstrated impaired NET degradation. Patients with GPA (p = 0.0045) and MPA (p = 0.005) had anti-NET IgG antibodies. Patients with TAK had anti-histone antibodies (p < 0.01), correlating with presence of NETs. Levels of TSP-1 were increased in all patients with vasculitis, and associated with NET formation. NET formation is a common process in vasculitides. Targeting NET formation or degradation could be potential therapeutic approaches for vasculitides. • Neutrophil extracellular traps (NETs) possess antimicrobial properties, but are also key players in the pathophysiology of many autoimmune diseases. • Although there is extensive literature about NET formation in ANCA-associated vasculitis, studies about neutrophil cell death in large-vessel vasculitis are limited. • Increased NET levels associated with platelet activation, along with impaired NET degradation are common features in ANCA-associated and large-vessel vasculitis. • Whilst more frequent in ANCA-associated vasculitis, some patients with large-vessel vasculitis also have antibodies targeting NETs. • Targeting both NET formation and degradation could be beneficial therapeutic approaches in the management of both ANCA-associated and large-vessel vasculitis. [ABSTRACT FROM AUTHOR]