Anti-endothelial cell IgG antibodies from patients with Wegener's granulomatosis bind to human endothelial cells in vitro and induce adhesion molecule expression and cytokine secretion.

Abstract

To elucidate the role of anti-endothelial cell antibodies (AECA) in vascular inflammation in patients with Wegener's granulomatosis (WG). IgG fractions from 3 AECA-positive WG patients, IgG from 3 AECA-negative WG patients, and IgG from healthy donors were tested for their ability to: a) bind to endothelial cells and to display complement-dependent or antibody-dependent cellular cytotoxicity, b) modulate cell membrane expression of adhesion molecules, as evaluated by cytofluorometry and by immunoenzymatic assay, and c) induce the secretion of interleukin-1 beta (IL-1 beta), IL-6, IL-8, and monocyte chemotactic protein 1 (MCP-1). We found that AECA IgG from WG patients do not display any significant cytotoxicity but are able to up-regulate the expression of E-selectin, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 and to induce the secretion of IL-1 beta, IL-6, IL-8, and MCP-1. AECA in patients with WG could play a potential pathogenetic role by activating endothelial cells, and thus facilitating leukocyte recruitment and adhesion to endothelial surfaces, rather than by displaying a cytotoxic activity.