ANTIENDOTHELIAL CELL IGG ANTIBODIES FROM PATIENTS WITH WEGENERS GRANULOMATOSIS BIND TO HUMAN ENDOTHELIAL-CELLS IN-VITRO AND INDUCE ADHESIONMOLECULE EXPRESSION AND CYTOKINE SECRETION

Objective. To elucidate the role of antiendothelial cell antibodies (A ECA) in vascular inflammation in patients with Wegener's granulomatosi s (WG). Methods. IgG fractions from 3 AECA-positive WG patients, IgG f rom 3 AECA-negative WG patients, and IgG from healthy donors were test ed for their ability to: a) bind to endothelial cells and to display c omplement-dependent or antibody-dependent cellular cytotoxicity, b) mo dulate cell membrane expression of adhesion molecules, as evaluated by cytofluorometry and by immunoenzymatic assay, and c) induce the secre tion of interleukin-1 beta (IL-1 beta), IL-6, IL-8, and monocyte chemo tactic protein 1 (MCP-1). Results. We found that AECA IgG from WG pati ents do not display any significant cytotoxicity but are able to up-re gulate 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. Conclusion. AECA in patients with WG could play a potential pathogenetic role by activating endothelial ce lls, and thus facilitating leukocyte recruitment and adhesion to endot hielial surfaces, rather than by displaying a cytotoxic activity.