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Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis.

Publication ,  Journal Article
Monach, PA; Warner, RL; Tomasson, G; Specks, U; Stone, JH; Ding, L; Fervenza, FC; Fessler, BJ; Hoffman, GS; Iklé, D; Kallenberg, CGM; Seo, P ...
Published in: Ann Rheum Dis
August 2013

OBJECTIVE: To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation. METHODS: Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6 months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS/WG)≥3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC). RESULTS: All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low. CONCLUSIONS: Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV.

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Published In

Ann Rheum Dis

DOI

EISSN

1468-2060

Publication Date

August 2013

Volume

72

Issue

8

Start / End Page

1342 / 1350

Location

England

Related Subject Headings

  • Tissue Inhibitor of Metalloproteinase-1
  • Severity of Illness Index
  • Rituximab
  • Remission Induction
  • ROC Curve
  • Proteins
  • Middle Aged
  • Matrix Metalloproteinase 3
  • Male
  • Immunologic Factors
 

Citation

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Monach, P. A., Warner, R. L., Tomasson, G., Specks, U., Stone, J. H., Ding, L., … Merkel, P. A. (2013). Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Ann Rheum Dis, 72(8), 1342–1350. https://doi.org/10.1136/annrheumdis-2012-201981
Monach, Paul A., Roscoe L. Warner, Gunnar Tomasson, Ulrich Specks, John H. Stone, Linna Ding, Fernando C. Fervenza, et al. “Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis.Ann Rheum Dis 72, no. 8 (August 2013): 1342–50. https://doi.org/10.1136/annrheumdis-2012-201981.
Monach PA, Warner RL, Tomasson G, Specks U, Stone JH, Ding L, et al. Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Ann Rheum Dis. 2013 Aug;72(8):1342–50.
Monach, Paul A., et al. “Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis.Ann Rheum Dis, vol. 72, no. 8, Aug. 2013, pp. 1342–50. Pubmed, doi:10.1136/annrheumdis-2012-201981.
Monach PA, Warner RL, Tomasson G, Specks U, Stone JH, Ding L, Fervenza FC, Fessler BJ, Hoffman GS, Iklé D, Kallenberg CGM, Krischer J, Langford CA, Mueller M, Seo P, St Clair EW, Spiera R, Tchao N, Ytterberg SR, Johnson KJ, Merkel PA. Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Ann Rheum Dis. 2013 Aug;72(8):1342–1350.

Published In

Ann Rheum Dis

DOI

EISSN

1468-2060

Publication Date

August 2013

Volume

72

Issue

8

Start / End Page

1342 / 1350

Location

England

Related Subject Headings

  • Tissue Inhibitor of Metalloproteinase-1
  • Severity of Illness Index
  • Rituximab
  • Remission Induction
  • ROC Curve
  • Proteins
  • Middle Aged
  • Matrix Metalloproteinase 3
  • Male
  • Immunologic Factors