OP0052 Microparticles as potential biomarkers of disease activity in anti-neutrophil cytoplasmic antibody – associated vasculitis

Abstract

Objectives: Increased levels of circulating microparticles (MPs), mainly of endothelial cell origin but also platelet derived, have been shown to correlate with autoinflammatory disease activity, such as anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). The aim was to evaluate levels of activity markers expressed on MPs from patients with AAV, during active disease and remission, compared to healthy control subjects. Method(s): Our study included 46 AAV patients and 23 healthy age-and gender-matched control subjects. We analysed the concentration of MPs in plasma by flow cytometry. MPs were phenotyped by expression of CD142 (tissue factor, TF), anti-H3cit (citrullinated histone 3 directed against neutrophil extracellular traps, NETs), antipentraxin3 (pentraxin3), HMGB1 (high-mobility group box 1 protein, HMGB1), anti-TWEAK (tumour necrosis factor-like weak inducer of apoptosis, TWEAK), anti-plasminogen (plasminogen), anti-C3a (C3a), and anti-C5a (C5a). Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS), where active disease was defined as BVAS >= 1 and inactive (remission) as BVAS = 0. Result(s): Half of the patient group (23) had active vasculitis (13 male, 10 female, mean age 61 +/- 14 years) and 23 had inactive disease (12 male, 11 female, mean age 64 +/- 13 years). Concentrations of MPs expressing TF, H3cit, pentraxin-3, and HMGB1 in active patients were significantly higher than in those in remission and healthy controls (p < 0.01 and p < 0.0001, respectively). MPs expressing C5a and C3a were significantly higher in both active and inactive patients compared to controls (p < 0.001). In addition, levels of MPs expressing C5a and C3a strongly correlated with BVAS in patients with active disease (r = 0.78, p < 0.0001; r = 0.5, p < 0.01, respectively), while there was no significant correlation between other explored markers and BVAS. Conclusion(s): Our results support the recently postulated role of the complement system in AAV pathogenesis and disease activity. Evaluated proteins expressed on MPs, especially C5a and C3a, could be used as potential biomarkers which may reflect inflammation and disease activity in AAV patients.