Anti-TNF-α therapy reduces endothelial cell activation in non-diabetic ankylosing spondylitis patients

Rheumatol Int. 2015 Dec;35(12):2069-78. doi: 10.1007/s00296-015-3314-1. Epub 2015 Jul 5.

Abstract

Endothelial dysfunction can be detected by the presence of elevated levels of biomarkers of endothelial cell activation. In this study, we aimed to establish whether correlations of these biomarkers with characteristics of patients with ankylosing spondylitis (AS) exist. We also studied the effect of anti-TNF-α therapy on these biomarkers. Serum sE-selectin, MCP-1 and sVCAM-1 levels were measured by ELISA in 30 non-diabetic AS patients undergoing anti-TNF-α therapy, immediately before and after an infusion of infliximab. Correlations of these biomarkers with clinical features, systemic inflammation, metabolic syndrome and other serum and plasma biomarkers of cardiovascular risk were studied. Potential changes in the concentration of these biomarkers following an infliximab infusion were also assessed. sE-selectin showed a positive correlation with CRP (p = 0.02) and with other endothelial cell activation biomarkers such as sVCAM-1 (p = 0.019) and apelin (p = 0.008). sVCAM-1 negatively correlated with BMI (p = 0.018), diastolic blood pressure (p = 0.008) and serum glucose (p = 0.04). sVCAM-1 also showed a positive correlation with VAS spinal pain (p = 0.014) and apelin (p < 0.001). MCP-1 had a negative correlation with LDL cholesterol (p = 0.026) and ESR (p = 0.017). Patients with hip involvement and synovitis and/or enthesitis in other peripheral joints showed higher levels of MCP-1 (p = 0.004 and 0.02, respectively). A single infliximab infusion led to a significant reduction in sE-selectin (p = 0.0015) and sVCAM-1 (p = 0.04). Endothelial dysfunction correlates with inflammation and metabolic syndrome features in patients with AS. A beneficial effect of the anti-TNF-α blockade on endothelial dysfunction, manifested by a reduction in levels of biomarkers of endothelial cell activation, was observed.

Keywords: Ankylosing spondylitis; Anti-TNF-α; Endothelial activation; MCP-1; sE-selectin; sVCAM-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / pharmacology*
  • Antirheumatic Agents / therapeutic use
  • Biomarkers / blood
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / metabolism
  • Chemokine CCL2 / blood
  • E-Selectin / blood
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Female
  • Humans
  • Infliximab / pharmacology*
  • Infliximab / therapeutic use
  • Male
  • Spondylitis, Ankylosing / complications
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Vascular Cell Adhesion Molecule-1 / blood

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Chemokine CCL2
  • E-Selectin
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Infliximab