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

Arthritis Rheum. 2011 Dec;63(12):3988-97. doi: 10.1002/art.30615.


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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / blood*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / drug therapy
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / physiopathology*
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antirheumatic Agents / therapeutic use
  • Biomarkers / blood
  • Blood Sedimentation
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Diagnosis, Differential
  • E-Selectin / blood*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Matrix Metalloproteinase 3 / blood*
  • Middle Aged
  • Neovascularization, Pathologic / blood*
  • Neovascularization, Pathologic / physiopathology
  • Remission Induction
  • Rituximab
  • Vascular System Injuries / blood*
  • Vascular System Injuries / physiopathology


  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Biomarkers
  • E-Selectin
  • Rituximab
  • C-Reactive Protein
  • Matrix Metalloproteinase 3