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.
Kümpers
Philipp
P
Department of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg Strasse 1, D-30625, Hannover, Germany. kuempers.philipp@mh-hannover.de
Hellpap
Julian
J
David
Sascha
S
Horn
Rüdiger
R
Leitolf
Holger
H
Haller
Hermann
H
Haubitz
Marion
M
D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D005260:Female; D005921:Glomerulonephritis / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012140:Respiratory Tract Diseases / Q000097:blood / Q000276:immunology; D014657:Vasculitis / Q000097:blood* / Q000276:immunology* / Q000473:pathology
D042702:Angiopoietin-2; D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers