부산대학교 도서관

To define mechanisms of vascular injury in Wegener's granulomatosis and microscopic polyarteritis, anti-endothelial cell antibodies (AECA) were sought in serum from 16ti patients, all of whom had anti-neutrophil cytoplasm antibodies (ANCA) detectable by indirect immunofluorescence. Using an ELISA with human umbilical vein endothelial cells (HUVEC), IgG AECA were demonstrated in 59% and IgM AECA in 68%, of patients. Pretreatment of HUVEC with tumour necrosis factor (TNF), IL-1 or interferon-gamma (IFN-γ) increased binding. Adsorption of AECA/ANCA containing serum with HUVEC or neutrophils demonstrated that AECA and ANCA recognized different targets, von Willebrand factor (vWf) antigen levels in the patient samples were markedly elevated, with a mean of 3.10 ± 1.89 U/ml (eontrol population mean 1.04 ± 0.36 U/ml), suggesting widespread endothelial eel) damage. Studies using an '"In-labelled HUVEC release assay with 29 AECA-containing sera did not demonstrate complement-mediated cytotoxicity. Even following activation of HUVEC with TNF. Four out of 16 AECA-containing sera tested showed antibody dependent cellular cytotoxicity with unfractionated peripheral blood mononuclear cells. These data suggest that patients with Wegener's granulomatosis or microscopic polyarteritis can develop AECA to constilutively expressed but cytokine modulated determinants on HUVFC. These antibodies do not appear to support complement-mediated cytotoxicity. but a proportion can support antibody dependent cellular cylotoxicity. suggesting that they may contribute lo vascular injury. [ABSTRACT FROM AUTHOR]