Membrane proteinase 3 expression on resting neutrophils as a pathogenic factor in PR3-ANCA-associated vasculitis

Antineutrophil cytoplasm autoantibody (ANCA)-associated small vessel vasculitides are systemic diseases characterized by chronic inflammation of blood vessels. These vasculitides are associated with the presence of ANCA which are, in most cases, directed towards proteinase 3 (PR3) or myeloperoxidase (MPO). In vitro and in vivo data have suggested a pathophysiological role in the ANCA-associated vasculitides, particularly based on the capacity of autoantibodies to bind and activate neutrophils. This review focuses on the role of constitutive expression of proteinase 3 on the membrane of resting neutrophils (mPR3). mPR3 can be expressed on the total population or on a subset of neutrophils and levels of mPR3 differ between individuals. The level of mPR3 on resting neutrophils and the percentage of mPR3 expressing neutrophils is stable in time for a given individual, suggesting a genetic determinant. Patients with ANCA-associated vasculitis have an increased constitutive expression of mPR3 on resting neutrophils compared to healthy controls. High levels of mPR3 on resting neutrophils are a risk factor for the development of relapses in patients with PR3-ANCA-associated vasculitis, probably by making resting neutrophils more susceptible for binding ANCA and induction of activation. As such, constitutive mPR3 expression on neutrophils seems another pathogenic factor in ANCA-associated vasculitis.