Circulating markers of vascular injury and angiogenesis in antineutrophil cytoplasmic antibody-associated vasculitis

Paul A. Monach, Gunnar Tomasson, Ulrich Specks, John H. Stone, David Cuthbertson, Jeffrey Krischer, Linna Ding, Fernando C. Fervenza, Barri J. Fessler, Gary S. Hoffman, David Ikle, Cees G.M. Kallenberg, Carol A. Langford, Mark Mueller, Philip Seo, E. William St.clair, Robert Spiera, Nadia Tchao, Steven R. Ytterberg, Yi Zhong GuRonald D. Snyder, Peter A. Merkel

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Objective To identify biomarkers that distinguish between active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner superior or complementary to established markers of systemic inflammation. Methods Markers of vascular injury and angiogenesis were measured before and after treatment in a large clinical trial in AAV: 163 subjects enrolled in the Rituximab in ANCA-Associated Vasculitis trial were screened for the present study. Serum levels of E-selectin, intercellular adhesion molecule 3 matrix metalloproteinase protein 1 (MMP-1), MMP-3, MMP-9, P-selectin, thrombomodulin, and vascular endothelial growth factor were measured at study screening (time of active disease) and at month 6. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels had been measured at the time of the clinical visit. The primary outcome measure was the difference in marker level between screening and month 6 among patients whose disease was in remission (Birmingham Vasculitis Activity Score for Wegener's granulomatosis [BVAS/WG] score of 0) at month 6. Results All patients had severe active vasculitis at screening (mean ± SD BVAS/WG score 8.6 ± 3.2). Among the 123 patients whose disease was clinically in remission at month 6, levels of all markers except E-selectin showed significant declines. MMP-3 levels were also higher among the 23 patients with active disease at month 6 than among the 123 patients whose disease was in remission. MMP-3 levels correlated weakly with ESR and CRP levels. Conclusion Many markers of vascular injury and angiogenesis are elevated in severe active AAV and decline with treatment, but MMP-3 appears to distinguish active AAV from remission better than the other markers studied. Further study of MMP-3 is warranted to determine its clinical utility in combination with conventional markers of inflammation and ANCA titers.

Original languageEnglish (US)
Pages (from-to)3988-3997
Number of pages10
JournalArthritis and rheumatism
Volume63
Issue number12
DOIs
StatePublished - Dec 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Monach, P. A., Tomasson, G., Specks, U., Stone, J. H., Cuthbertson, D., Krischer, J., Ding, L., Fervenza, F. C., Fessler, B. J., Hoffman, G. S., Ikle, D., Kallenberg, C. G. M., Langford, C. A., Mueller, M., Seo, P., St.clair, E. W., Spiera, R., Tchao, N., Ytterberg, S. R., ... Merkel, P. A. (2011). Circulating markers of vascular injury and angiogenesis in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis and rheumatism, 63(12), 3988-3997. https://doi.org/10.1002/art.30615