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

Abstract

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.