Subclinical gut inflammation in spondyloarthritis is associated with a pro-angiogenic intestinal mucosal phenotype

Ann Rheum Dis. 2011 Nov;70(11):2044-8. doi: 10.1136/ard.2010.149229. Epub 2011 Aug 26.

Abstract

Background: Vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF) are major regulators of pathological angiogenesis, which is a prominent feature of both Crohn's disease (CD) and peripheral synovitis in spondyloarthritis.

Objective: To investigate the presence of VEGF-A and PlGF in the gut of spondyloarthritis patients and to link this finding with subclinical gut inflammation in these patients.

Methods: Intestinal biopsies from healthy controls, CD patients, spondyloarthritis patients with or without subclinical gut inflammation and rheumatoid arthritis (RA) patients were stained for VEGF-A, PlGF, CD31 and vascular cell adhesion molecule 1 (VCAM-1) and digitally analysed.

Results: Spondyloarthritis patients with subclinical gut inflammation had markedly increased intestinal VEGF-A expression (p<0.001), mucosal vascularisation (p<0.001) and VCAM-1 expression (p<0.01) compared with healthy controls and RA patients, which, unlike in CD patients, was also seen when the gut inflammation was in a quiescent state. PlGF expression was highly increased in the subclinically inflamed gut of spondyloarthritis (p<0.01 compared with healthy controls), but not at all in CD.

Conclusion: A pro-angiogenic intestinal phenotype is observed in spondyloarthritis patients with quiescent chronic gut inflammation. This favours an environment for enhanced trafficking of immune cells in this subpopulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Case-Control Studies
  • Colitis / etiology*
  • Colitis / metabolism
  • Colitis / pathology
  • Crohn Disease / metabolism
  • Crohn Disease / pathology
  • Endothelium, Vascular / metabolism
  • Humans
  • Ileitis / etiology*
  • Ileitis / metabolism
  • Ileitis / pathology
  • Intestinal Mucosa / blood supply*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Neovascularization, Pathologic / etiology*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Placenta Growth Factor
  • Pregnancy Proteins / metabolism
  • Spondylarthritis / complications*
  • Spondylarthritis / metabolism
  • Spondylarthritis / pathology
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • PGF protein, human
  • Pregnancy Proteins
  • VEGFA protein, human
  • Vascular Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Placenta Growth Factor