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. 2011 Jun;38(6):1048-54.
doi: 10.3899/jrheum.100735. Epub 2011 Mar 16.

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

Gunnar Tomasson  1 , Michael Lavalley, Kahraman Tanriverdi, Javier D Finkielman, John C Davis Jr, Gary S Hoffman, W Joseph McCune, E William St Clair, Ulrich Specks, Robert Spiera, John H Stone, Jane E Freedman, Peter A Merkel; Wegener's Granulomatosis Etanercept Trial (WGET) Research Group
Collaborators, Affiliations

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

Gunnar Tomasson et al. J Rheumatol. 2011 Jun.

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.

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Figures

Figure 1
Figure 1
Longitudinal changes of marker levels. Nonparametric smoothing of marker levels at several timepoints in the study. X axis represents different timepoints, and the Y axis standardized marker levels after subtraction of the baseline value (all baseline values set to zero). Broken X axis represents that flares did not occur at the same times for all study subjects.
See this image and copyright information in PMC

References

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