Increased levels of BLyS and sVCAM-1 in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV)

Clin Exp Rheumatol. Jan-Feb 2010;28(1 Suppl 57):62-6.

Abstract

Objectives: Anti-neutrophil antibodies (ANCA)-associated vasculitides (AAV) comprise different forms of small vessel vasculitis characterised by B-cell driven autoimmune processes and endothelial cell activation. Aim of this study was to correlate markers of B- and endothelial cell activation with clinical manifestations of disease in AAV.

Methods: Consecutive serum samples of patients fulfilling the Chapel Hill Consensus Conference (CHCC) and American College of Rheumatology (ACR) criteria for AAV and healthy donors were used for the determination of ANCA, B-lymphocyte stimulator (BLyS), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) levels using enzyme-linked immunosorbent assay (ELISA). Subset and follow-up analyses were performed in cytoplasmatic ANCA (C-ANCA) or perinuclear ANCA (P-ANCA) positive patients with respect to change in ANCA-titres during the course of disease.

Results: Levels of sVCAM-1 were elevated in all patient groups with vasculitis compared to healthy controls. In contrast, significantly increased levels of BLyS were only observed in patients with Wegener's granulomatosis (WG), but not in patients with microscopic polyangiitis (mPAN)/Churg-Strauss-syndrome (CSS). Remarkably, there were no differences in the levels of sE-selectin between the vasculitis groups and healthy controls. In follow-up analysis, a significant correlation was shown for sE-Selectin and P-ANCA titres as well as sVCAM-1 levels. Furthermore, a strong correlation was detected for sVCAM-1 and creatinine levels. Interestingly, sE-selectin levels and C-ANCA titres were negatively correlated.

Conclusions: Enhanced levels of sVCAM-1 represent a marker for endothelial cell activation in AAV. The observed correlation between sVCAM-1 and creatinine levels might indicate the influence of the vasculitic process on renal function. Signalling pathways for B-cells provided by BLyS could play a significant role in the pathogenesis of WG.

MeSH terms

  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / blood*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology*
  • B-Cell Activating Factor / blood*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Biomarkers / blood*
  • E-Selectin / blood
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Follow-Up Studies
  • Humans
  • Signal Transduction / immunology
  • Solubility
  • Vascular Cell Adhesion Molecule-1 / blood*

Substances

  • B-Cell Activating Factor
  • Biomarkers
  • E-Selectin
  • TNFSF13B protein, human
  • Vascular Cell Adhesion Molecule-1