title: Circulating angiopoietin-2 as a biomarker in ANCA-associated vasculitis.
abstract: The endothelial-specific Angiopoietin-Tie2 ligand-receptor system is an important regulator of endothelial activation. Binding of angiopoietin-2 (Ang-2) to Tie2 receptor renders the endothelial barrier responsive to pro-inflammatory cytokines. We previously showed that circulating Ang-2 correlated with disease severity in a small cohort of critically ill patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. The current study reassessed Ang-2 as a biomarker of disease activity and relapse in AAV. Circulating Ang-2 was measured in 162 patients with severe AAV (BVAS/WG≥3, with or without glomerulonephritis) in a clinical trial. Ang-2 levels during active AAV were compared to levels in the same patients during remission (BVAS/WG = 0). Levels in clinical subsets of AAV were compared, and association with future disease course was assessed. Ang-2 levels were elevated in severe disease (median 3.0 ng/ml, interquartile range 1.9-4.4) compared to healthy controls (1.2, 0.9-1.5). However, they did not reliably decline with successful treatment (median 2.6 ng/ml, interquartile range 1.9-3.8, median change -0.1). Ang-2 correlated weakly with BVAS/WG score (r = 0.17), moderately with markers of systemic inflammation (r = 0.25-0.41), and inversely with renal function (r = -0.36). Levels were higher in patients with glomerulonephritis, but levels adjusted for renal dysfunction were no different in patients with or without glomerulonephritis. Levels were higher in patients with newly diagnosed AAV and lower in patients in whom treatment had recently been started. Ang-2 levels during active disease did not predict response to treatment, and Ang-2 levels in remission did not predict time to flare. Thus, Ang-2 appears to have limited practical value in AAV as a biomarker of disease activity at time of measurement or for predicting future activity.
authors.affiliation: Section of Rheumatology, Department of Medicine, School of Medicine, Vasculitis Center, Boston University, Boston, Massachusetts, United States of America. pmonach@bu.edu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Monach
authors.forename: Philipp
authors.initials: P
authors.lastname: Kümpers
authors.forename: Alexander
authors.initials: A
authors.lastname: Lukasz
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tomasson
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.forename: David
authors.initials: D
authors.lastname: Cuthbertson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Krischer
authors.forename: Simon
authors.initials: S
authors.lastname: Carette
authors.forename: Linna
authors.initials: L
authors.lastname: Ding
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.forename: David
authors.initials: D
authors.lastname: Iklé
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: Nader A
authors.initials: NA
authors.lastname: Khalidi
authors.forename: Carol A
authors.initials: CA
authors.lastname: Langford
authors.forename: Philip
authors.initials: P
authors.lastname: Seo
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.forename: Robert
authors.initials: R
authors.lastname: Spiera
authors.forename: Nadia
authors.initials: N
authors.lastname: Tchao
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ytterberg
authors.forename: Marion
authors.initials: M
authors.lastname: Haubitz
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
mesh_terms: D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood*; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012074:Remission Induction
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers