title: Circulating markers of vascular injury and angiogenesis in antineutrophil cytoplasmic antibody-associated vasculitis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Monach
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tomasson
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.forename: David
authors.initials: D
authors.lastname: Cuthbertson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Krischer
authors.forename: Linna
authors.initials: L
authors.lastname: Ding
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.forename: Barri J
authors.initials: BJ
authors.lastname: Fessler
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.forename: David
authors.initials: D
authors.lastname: Ikle
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: Carol A
authors.initials: CA
authors.lastname: Langford
authors.forename: Mark
authors.initials: M
authors.lastname: Mueller
authors.forename: Philip
authors.initials: P
authors.lastname: Seo
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.forename: Robert
authors.initials: R
authors.lastname: Spiera
authors.forename: Nadia
authors.initials: N
authors.lastname: Tchao
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ytterberg
authors.forename: Yi-Zhong
authors.initials: YZ
authors.lastname: Gu
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Snyder
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D019040:E-Selectin / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood* / Q000503:physiopathology; D012074:Remission Induction; D000069283:Rituximab; D057772:Vascular System Injuries / Q000097:blood* / Q000503:physiopathology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D015415:Biomarkers; D019040:E-Selectin; D000069283:Rituximab; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3