Selective up-regulation of the soluble pattern-recognition receptor pentraxin 3 and of vascular endothelial growth factor in giant cell arteritis: relevance for recent optic nerve ischemia

Arthritis Rheum. 2012 Mar;64(3):854-65. doi: 10.1002/art.33411.

Abstract

Objective: To assess local expression and plasma levels of pentraxin 3 (PTX3) in patients with giant cell arteritis (GCA).

Methods: Plasma and serum samples were obtained from 75 patients with GCA (20 of whom had experienced optic nerve ischemia in the previous 3 weeks and 24 of whom had experienced symptom onset in the previous 6 months and had no history of optic nerve ischemia) and 63 controls (35 age-matched healthy subjects, 15 patients with rheumatoid arthritis, and 13 patients with chronic stable angina). In 9 patients in whom GCA was recently diagnosed, circulating levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p70, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1α (MIP-1α), CCL4/MIP-1β, CCL11/eotaxin, CXCL9/monokine induced by interferon-γ, CXCL10/interferon-γ-inducible 10-kd protein, tumor necrosis factor α (TNFα), interferon-γ, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor, and FasL were measured via a multiplexed cytometric assay. PTX3 and VEGF concentrations were assessed by enzyme-linked immunosorbent assay. PTX3 and CD68 expression were determined by immunohistochemistry and immunofluorescence on temporal artery samples.

Results: GCA patients with very recent optic nerve ischemia had significantly higher PTX3 and VEGF levels compared to other GCA patients and controls. GCA patients with a disease duration of <6 months had significantly higher PTX3 levels compared to other GCA patients and controls. Immunohistochemistry revealed selective PTX3 expression in the wall of inflamed arteries.

Conclusion: Our findings indicate that local expression of PTX3 is a feature of vascular inflammation in GCA; elevated circulating levels of PTX3 identify patients with very recent optic nerve ischemia or a recent diagnosis. Optic nerve ischemia is also associated with increased circulating VEGF levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • C-Reactive Protein / analysis
  • C-Reactive Protein / biosynthesis*
  • Cytokines / metabolism
  • Female
  • Giant Cell Arteritis / complications
  • Giant Cell Arteritis / diagnosis
  • Giant Cell Arteritis / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Optic Neuropathy, Ischemic / diagnosis
  • Optic Neuropathy, Ischemic / etiology
  • Optic Neuropathy, Ischemic / metabolism*
  • Serum Amyloid P-Component / analysis
  • Serum Amyloid P-Component / biosynthesis*
  • Temporal Arteries / metabolism*
  • Temporal Arteries / pathology
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Cytokines
  • Serum Amyloid P-Component
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • PTX3 protein
  • C-Reactive Protein