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

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 63; no. 12; pp. 3988 - 3997
• Main Authors: Monach, Paul A., Tomasson, Gunnar, Specks, Ulrich, Stone, John H., Cuthbertson, David, Krischer, Jeffrey, Ding, Linna, Fervenza, Fernando C., Fessler, Barri J., Hoffman, Gary S., Ikle, David, Kallenberg, Cees G. M., Langford, Carol A., Mueller, Mark, Seo, Philip, St.Clair, E. William, Spiera, Robert, Tchao, Nadia, Ytterberg, Steven R., Gu, Yi‐Zhong, Snyder, Ronald D., Merkel, Peter A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2011; Wiley; Wiley Subscription Services, Inc
• Subjects: 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; Biological and medical sciences; Biomarkers - blood; Blood Sedimentation; C-Reactive Protein - metabolism; Case-Control Studies; Diagnosis, Differential; Diseases of the osteoarticular system; E-Selectin - blood; Female; Follow-Up Studies; Humans; Male; Matrix Metalloproteinase 3 - blood; Medical sciences; Middle Aged; Neovascularization, Pathologic - blood; Neovascularization, Pathologic - physiopathology; Remission Induction; Rituximab; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Vascular System Injuries - blood; Vascular System Injuries - physiopathology; Vascular disease; Angiogenesis; Vasculitis; Antineutrophil cytoplasmic antibody; Blood vessel; Rheumatology; Cardiovascular disease
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• 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.