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Circulating Angiopoietin-2 as a Biomarker in ANCA-Associated Vasculitis

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 w...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261176/
https://www.ncbi.nlm.nih.gov/pubmed/22279570
http://dx.doi.org/10.1371/journal.pone.0030197
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author 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.
author_facet 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.
author_sort Monach, Paul A.
collection PubMed
description 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.
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spelling pubmed-32611762012-01-25 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. PLoS One Research Article 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. Public Library of Science 2012-01-18 /pmc/articles/PMC3261176/ /pubmed/22279570 http://dx.doi.org/10.1371/journal.pone.0030197 Text en Monach et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
title Circulating Angiopoietin-2 as a Biomarker in ANCA-Associated Vasculitis
title_full Circulating Angiopoietin-2 as a Biomarker in ANCA-Associated Vasculitis
title_fullStr Circulating Angiopoietin-2 as a Biomarker in ANCA-Associated Vasculitis
title_full_unstemmed Circulating Angiopoietin-2 as a Biomarker in ANCA-Associated Vasculitis
title_short Circulating Angiopoietin-2 as a Biomarker in ANCA-Associated Vasculitis
title_sort circulating angiopoietin-2 as a biomarker in anca-associated vasculitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261176/
https://www.ncbi.nlm.nih.gov/pubmed/22279570
http://dx.doi.org/10.1371/journal.pone.0030197
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