Relationship between markers of platelet activation and inflammation with disease activity in Wegener's granulomatosis

Gunnar Tomasson, Michael LaValley, Kahraman Tanriverdi, Javier D. Finkielman, John C. Davis, Gary S. Hoffman, W. Joseph McCune, E. William St. Clair, Ulrich Specks, Robert Spiera, John H. Stone, Jane E. Freedman, Peter A. Merkel

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Objective. There remains a need for biomarkers to guide therapy in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our objective was to determine whether measures of platelet activation or inflammation are associated with disease activity in Wegener's granulomatosis (WG). Methods. Study subjects were participants in a clinical trial. Soluble CD40 ligand (sCD40L), C-reactive protein, interleukin 6 (IL-6), IL-8, monocyte chemoattractant protein 1 (MCP-1), P-selectin, vascular endothelial growth factor, and proteinase 3 (PR3)-specific ANCA were measured by ELISA using plasma samples obtained at baseline (active disease), at remission, and prior to, during, and after first flares. Disease activity was assessed by the Birmingham Vasculitis Activity Score for WG (BVAS/WG). Association of biomarkers with disease activity was determined with conditional logistic and linear regression. Results. Over a mean followup of 27 months, 180 subjects underwent 2044 visits; markers were measured in 563 samples. Longitudinally, all markers other than IL-6 were associated with disease activity. The strongest associations for active disease at baseline versus remission were observed for sCD40L (OR 4.72, 95% CI 2.47-9.03), P-selectin (OR 6.26, 95% CI 2.78-14.10), PR3-ANCA (OR 9.41, 4.03-21.99), and inversely for MCP-1 (OR 0.36, 95% CI 0.22-0.57). BVAS/WG increased by 0.80 (95% CI 0.44-1.16), 0.83 (95% CI 0.42-1.25), and 0.81 (95% CI 0.48-1.15) per unit-increase in PR3-ANCA, sCD40L, and P-selectin, respectively; and decreased by 1.54 (95% CI 0.96-2.12) per unit-increase in MCP-1. Conclusion. Cytokines arising from within the circulation, including those of platelet activation, correlate with disease activity in WG. The Journal of Rheumatology

Original languageEnglish (US)
Pages (from-to)1048-1054
Number of pages7
JournalJournal of Rheumatology
Volume38
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • Biomarkers
  • Disease activity
  • Vasculitis
  • Wegener's granulomatosis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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