Background Systemic necrotizing vasculitis (SNV) is characterised by destructive and inflammatory changes in the vessels. Binding of autoantibodies and immune complexes on the surface of endothelial cells stimulates the synthesis… Click to show full abstract
Background Systemic necrotizing vasculitis (SNV) is characterised by destructive and inflammatory changes in the vessels. Binding of autoantibodies and immune complexes on the surface of endothelial cells stimulates the synthesis of endothelin-1 (ET-1), which leads to activation of macrophages and adhesion of neutrophils, remodelling of the vascular wall and its damage. Objectives To evaluate the serum level of ET-1 in patients with SNV and the possibility of its using for the diagnosis of SNV and involvement of individual organs. Methods The study included 36 patients with SNV (polyarthritis nodosa – 8, ANCA – associated vasculitis – 28) and healthy controls (n=26). Clinical activities of patients were calculated according to the Birmingham Vasculitis Activity Score (BVAS). All patients had active disease (BVAS >11). The serum levels of ET-1 (pmol/L) were determined by immunoassay analysis using the kits of Biomedica. The outcomes of this study were the differences in marker levels between patients with active SNV and healthy controls, patients with different forms of vasculitis, with varying degrees of BVAS activity, with involvement different organs and systems estimated by analysis of the absolute changes in marker levels and the areas under receiver operating characteristic (ROC) curves (AUC). Results The level of ET-1 (M±σ) in the general group of patients with SNV was 0.31±0.24 and did not differ significantly from the control group (0.27±0.10, p>0.05). At the same time, in patients who did not receive at screening glucocorticoids and cytotoxic agents (n=9), it was significantly elevated (0.62±0.58, p=0.03). However, ROC analysis indicated the moderate sensitivity (67%) and the low specificity (48%) of ET-1 for diagnosis of SNV. There were no significant differences in the levels of ET-1 between patients with different forms of vasculitis and with varying degrees of BVAS activity. In the analysis of the values of the ET-1 depending on the involvement of different organs and systems, it was found that only in patients with kidney involvement (n=15) its level (0.40±0.33) was significantly higher compared with patients without kidney involvement (0.28±0.22, p=0.04) and control group (p<0.01). ROC analysis showed that the AUC for ET-1 is 0.75±0.10 (p=0.004), which indicates acceptable capacity for ET-1 differentiate groups of patients with kidney involvement and patients without kidney involvement (sensitivity – 80.0%, specificity – 78.3%). Conclusions The serum levels of ET-1 were elevated in patients with SNV with kidney involvement (48% compared to healthy controls and 43% compared with patients without kidney involvement), which can be used for diagnostic purposes. Disclosure of Interest None declared
               
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