Abstract
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). Forty-six patients with AAV and 23 age- and sex-matched healthy controls were included. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). 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). Serum levels of PTX3, sTWEAK, and HMGB1 were also determined. Twenty-three patients had active vasculitis (BVAS ≥ 1). 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. MPO+MPs expressing either PTX3 or HMGB1 were associated with BVAS (r = 0.5, p < 0.001; r = 0.3, p = 0.04, respectively). 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). Serum levels of sTWEAK and HMGB1 did not differ between patients and controls. Concentration of MPO+MPs is increased in plasma from AAV patients compared to healthy individuals. PTX3 in serum as well as PTX3 and HMGB1 expressed on MPO+MPs were associated with disease activity in the investigated patients.Key messagesMyeloperoxidase-positive microparticles (MPO+MPs) are increased in plasma from patients with ANCA-associated vasculitis.Concentrations of MPO+MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls.MPO+MPs expressing PTX3 and HMGB1 are associated with disease activity in ANCA-associated vasculitis.
Highlights
Antineutrophil cytoplasmic antibodies (ANCAs) are serologic hallmarks of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a group of multisystem disorders characterized by pauci-immune necrotizing vasculitis affecting small- to medium-sized blood vessels
We have demonstrated significantly increased concentrations of myeloperoxidase-positive microparticles (MPO+MPs) expressing inflammatory biomarkers PTX3, high mobility group box 1 protein (HMGB1), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in plasma samples from AAV patients compared to healthy controls, while concentrations of MPO+MPs expressing PTX3 and HMGB1 were significantly higher in active AAV compared to patients in remission
It seems from the present results that presence of PTX3, HMGB1, and TWEAK on MPO+MPs was not associated to renal involvement in active AAV patients
Summary
Antineutrophil 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. 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. ANCAs are predominantly IgG autoantibodies directed against neutrophil cytoplasmic components, in particular proteinase 3 (PR3) and myeloperoxidase (MPO) [1]. 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 [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
