We have recently demonstrated increased levels of MPs expressing MPO and complement components C3a and C5a in patients with AAV, postulating that a majority of MPs are of neutrophil origin, although monocytes also have been shown to express MPO in lower concentrations. It has been shown that neutrophil-derived MPs contain active myeloperoxidase (MPO), an enzyme responsible for activation of endothelial cells, injury, and development of vascular lesions in AAV. MPs are submicron membranous vesicles, which could exert pro-inflammatory and pro-coagulant stimuli in a course of vasculitis. ĭuring activation and apoptosis, neutrophils release microparticles (MPs), also known as extracellular vesicles. Complement activation, especially via the alternative pathway, acts as positive feedback amplification of neutrophil activation, resulting in the aggressive necrotizing inflammation in ANCA-associated diseases. Priming, degranulation, and release of neutrophil extracellular traps (NETs) occurs, whereby neutrophils undergo apoptosis and necrosis.
There is a growing body of evidence that ANCA-induced neutrophil activation plays an essential role in the pathogenesis of AAV. ANCAs are predominantly IgG autoantibodies directed against neutrophil cytoplasmic components, in particular proteinase 3 (PR3) and myeloperoxidase (MPO). These conditions are associated with an increased risk of irreversible organ damage, especially in the kidneys, lungs and central nervous system, as well as with an increased mortality risk. PTX3 in serum as well as PTX3 and HMGB1 expressed on MPO +MPs were associated with disease activity in the investigated patients.Īntineutrophil cytoplasmic antibodies (ANCAs) are serologic hallmarks of ANCA-associated vasculitis (AAV), a group of multisystem disorders characterized by pauci-immune necrotizing vasculitis affecting small- to medium-sized blood vessels. Concentration of MPO +MPs is increased in plasma from AAV patients compared to healthy individuals.
Serum levels of sTWEAK and HMGB1 did not differ between patients and controls. Significantly higher serum PTX3 levels were found in active- than in inactive AAV ( p < 0.001), correlating strongly with BVAS ( r = 0.7, p < 0.001). MPO +MPs expressing either PTX3 or HMGB1 were associated with BVAS ( r = 0.5, p < 0.001 r = 0.3, p = 0.04, respectively). Concentrations of MPO +MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls ( p < 0.001, p < 0.01, p < 0.001, respectively), while concentrations of PTX3 + and HMGB1 +MPO +MPs were significantly higher in active AAV compared to patients in remission. Twenty-three patients had active vasculitis (BVAS ≥ 1). Serum levels of PTX3, sTWEAK, and HMGB1 were also determined. MPs were analyzed in citrate plasma by flow cytometry and phenotyped based on MPO expression and co-expression of pentraxin-3 (PTX3), high mobility group box 1 protein (HMGB1), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). Forty-six patients with AAV and 23 age- and sex-matched healthy controls were included.
To investigate presence of circulating myeloperoxidase-positive microparticles (MPO +MPs) in relation to disease activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
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