Circulating angiopoietin-2 is a marker and potential mediator of endothelial cell detachment in ANCA-associated vasculitis with renal involvement

Background. The endothelial-specific angiopoietin (Ang)-Tie ligand-receptor system has been identified as a non-redundant regulator of endothelial cell detachment in vitro. Binding of circulating angiopoietin-2 (Ang-2) to the Tie2 receptor antagonizes Tie2 signalling and leads to disassembly of cell-cell junctions. Here, we ask whether circulating Ang-2 correlates with the severity of endothelial damage in ANCA-associated vasculitis (AAV) with renal involvement. Methods. Ang-2 was measured in sera obtained from 45 patients with AAV and 20 healthy controls by in-house ELISA. The disease activity was monitored by BVAS and the enumeration of circulating endothelial cells (CECs). Results. Ang-2 was significantly elevated in active AAV with renal involvement compared to controls and patients in remission. In contrast, Ang-2 was normal in patients with active granulomatous disease limited to the respiratory tract. Linear regression analysis demonstrated a strong association of Ang-2 with BVAS (r(s)(2) = 0.49 P < 0.0001) and the number of CECs (r(s)(2) = 0.48 P < 0.001). An Ang-2 cut-off value > 4.15 ng/ml for a positive result yielded 100% specificity and 65% sensitivity for active systemic vasculitis. The positive predictive value was 99% and the negative predictive value 84%. Conclusions. Circulating Ang-2 is elevated and closely correlates with BVAS and CEC numbers in AAV with renal involvement. These data indicate that Ang-2 might be a potential mediator of endothelial cell detachment in AAV.