Circulating angiopoietin-2 as a biomarker in ANCA-associated vasculitis

Paul A. Monach, Philipp Kümpers, Alexander Lukasz, Gunnar Tomasson, Ulrich Specks, John H. Stone, David Cuthbertson, Jeffrey Krischer, Simon Carette, Linna Ding, Gary S. Hoffman, David Iklé, Cees G M Kallenberg, Nader A. Khalidi, Carol A. Langford, Philip Seo, E. William St. Clair, Robert Spiera, Nadia Tchao, Steven R YtterbergMarion Haubitz, Peter A. Merkel

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere30197
JournalPLoS One
Volume7
Issue number1
DOIs
StatePublished - Jan 18 2012

Fingerprint

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Angiopoietin-2
vasculitis
Antineutrophil Cytoplasmic Antibodies
Biomarkers
neutrophils
biomarkers
antibodies
glomerulonephritis
Glomerulonephritis
TIE-2 Receptor
remission
angiopoietin-2
Angiopoietins
Kidney
receptors
relapse
renal function
disease course
Critical Illness

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Monach, P. A., Kümpers, P., Lukasz, A., Tomasson, G., Specks, U., Stone, J. H., ... Merkel, P. A. (2012). Circulating angiopoietin-2 as a biomarker in ANCA-associated vasculitis. PLoS One, 7(1), [e30197]. https://doi.org/10.1371/journal.pone.0030197

Circulating angiopoietin-2 as a biomarker in ANCA-associated vasculitis. / Monach, Paul A.; Kümpers, Philipp; Lukasz, Alexander; Tomasson, Gunnar; Specks, Ulrich; Stone, John H.; Cuthbertson, David; Krischer, Jeffrey; Carette, Simon; Ding, Linna; Hoffman, Gary S.; Iklé, David; Kallenberg, Cees G M; Khalidi, Nader A.; Langford, Carol A.; Seo, Philip; St. Clair, E. William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Haubitz, Marion; Merkel, Peter A.

In: PLoS One, Vol. 7, No. 1, e30197, 18.01.2012.

Research output: Contribution to journalArticle

Monach, PA, Kümpers, P, Lukasz, A, Tomasson, G, Specks, U, Stone, JH, Cuthbertson, D, Krischer, J, Carette, S, Ding, L, Hoffman, GS, Iklé, D, Kallenberg, CGM, Khalidi, NA, Langford, CA, Seo, P, St. Clair, EW, Spiera, R, Tchao, N, Ytterberg, SR, Haubitz, M & Merkel, PA 2012, 'Circulating angiopoietin-2 as a biomarker in ANCA-associated vasculitis', PLoS One, vol. 7, no. 1, e30197. https://doi.org/10.1371/journal.pone.0030197
Monach PA, Kümpers P, Lukasz A, Tomasson G, Specks U, Stone JH et al. Circulating angiopoietin-2 as a biomarker in ANCA-associated vasculitis. PLoS One. 2012 Jan 18;7(1). e30197. https://doi.org/10.1371/journal.pone.0030197
Monach, Paul A. ; Kümpers, Philipp ; Lukasz, Alexander ; Tomasson, Gunnar ; Specks, Ulrich ; Stone, John H. ; Cuthbertson, David ; Krischer, Jeffrey ; Carette, Simon ; Ding, Linna ; Hoffman, Gary S. ; Iklé, David ; Kallenberg, Cees G M ; Khalidi, Nader A. ; Langford, Carol A. ; Seo, Philip ; St. Clair, E. William ; Spiera, Robert ; Tchao, Nadia ; Ytterberg, Steven R ; Haubitz, Marion ; Merkel, Peter A. / Circulating angiopoietin-2 as a biomarker in ANCA-associated vasculitis. In: PLoS One. 2012 ; Vol. 7, No. 1.
@article{f964ba84e8244124bf65901044db410c,
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.",
author = "Monach, {Paul A.} and Philipp K{\"u}mpers and Alexander Lukasz and Gunnar Tomasson and Ulrich Specks and Stone, {John H.} and David Cuthbertson and Jeffrey Krischer and Simon Carette and Linna Ding and Hoffman, {Gary S.} and David Ikl{\'e} and Kallenberg, {Cees G M} and Khalidi, {Nader A.} and Langford, {Carol A.} and Philip Seo and {St. Clair}, {E. William} and Robert Spiera and Nadia Tchao and Ytterberg, {Steven R} and Marion Haubitz and Merkel, {Peter A.}",
year = "2012",
month = "1",
day = "18",
doi = "10.1371/journal.pone.0030197",
language = "English (US)",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Circulating angiopoietin-2 as a biomarker in ANCA-associated vasculitis

AU - Monach, Paul A.

AU - Kümpers, Philipp

AU - Lukasz, Alexander

AU - Tomasson, Gunnar

AU - Specks, Ulrich

AU - Stone, John H.

AU - Cuthbertson, David

AU - Krischer, Jeffrey

AU - Carette, Simon

AU - Ding, Linna

AU - Hoffman, Gary S.

AU - Iklé, David

AU - Kallenberg, Cees G M

AU - Khalidi, Nader A.

AU - Langford, Carol A.

AU - Seo, Philip

AU - St. Clair, E. William

AU - Spiera, Robert

AU - Tchao, Nadia

AU - Ytterberg, Steven R

AU - Haubitz, Marion

AU - Merkel, Peter A.

PY - 2012/1/18

Y1 - 2012/1/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84855978485&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855978485&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0030197

DO - 10.1371/journal.pone.0030197

M3 - Article

C2 - 22279570

AN - SCOPUS:84855978485

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e30197

ER -