title: Relationship between markers of platelet activation and inflammation with disease activity in Wegener's granulomatosis.
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.
  
  
  CONCLUSIONS
  Cytokines arising from within the circulation, including those of platelet activation, correlate with disease activity in WG.
authors.affiliation: Boston University (BU) School of Medicine, and Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tomasson
authors.forename: Michael
authors.initials: M
authors.lastname: Lavalley
authors.forename: Kahraman
authors.initials: K
authors.lastname: Tanriverdi
authors.forename: Javier D
authors.initials: JD
authors.lastname: Finkielman
authors.forename: John C
authors.initials: JC
authors.lastname: Davis
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
authors.forename: Robert
authors.initials: R
authors.lastname: Spiera
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.forename: Jane E
authors.initials: JE
authors.lastname: Freedman
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005500:Follow-Up Studies; D014890:Granulomatosis with Polyangiitis / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood; D053146:Myeloblastin / Q000097:blood; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D012189:Retrospective Studies; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D016209:Interleukin-8; D019007:P-Selectin; D042461:Vascular Endothelial Growth Factor A; D023201:CD40 Ligand; D002097:C-Reactive Protein; D053146:Myeloblastin