P273	Induction of endothelial cell activation and apoptosis by IgG antibodies from SLE patients and non-SLE patients with nefropathy: a role for Anti-Endothelial-Cell (AEC)-Antibodies and non-AEC-Antibodies.
1A.Duijvestijn, 2L.Debrus-Palmans, 1M.Vroomen, 2P.van Paassen, 2J.W.Cohen Tervaert
1University of Maastricht, Maastricht, NL; 2Academic Hospital Maastricht, Maastricht, NL.

Vasculopathy is a major clinical aspect in patients with systemic lupus erythematosus (SLE). Anti-endothelial cell antibodies (AECAs) are putative candidates in the pathogenesis of this vasculopathy. We have studied a group of SLE patients and a group of non-SLE patients both with nefropathy for the reactivity of AECAs, and non-AECAs with endothelial cells (EC) in vitro. IgG fractions isolated from sera of the 2 patients groups and a healthy control group were tested for the presence of AECA-antibodies using a Human-Umbilical-Endothelial-Cell (HUVEC) cyto-ELISA. Induction of apoptosis in HUVEC by IgGs was measured by FACS analysis of hypoploid apoptotic cells using DNA-staining. Induction of adhesion molecules in HUVEC by IgGs was measured by FACS analysis of E-Selectin, ICAM-1 and VCAM-1 expression. Induction of apoptosis in HUVEC by IgGs was found for both patient groups (mean apoptosis values 35.6 – 53.3 %, N=3; p<0.01). No induction of apoptosis was seen by IgGs from the control group, values were similar as in HUVEC without IgG incubation (23.8 – 37.0 %) Comparison between AECA+ and AECA- patients in both patient groups showed no difference in apoptosis induction. Highest induction was found for IgGs from AECA+ patients. [GRAPHIC Both patient groups, but not the control group, showed IgG-induced expression of E-selectin, ICAM-1 and VCAM-1 in HUVEC. No difference between IgGs from AECA+ and AECA- patients was observed. The highest adhesion molecule induction was induced by IgGs from AECA+ patients. Some of the high apoptosis-inducing IgGs also induced high adhesion molecule expression. We conclude that SLE as well as non-SLE patients with nefropathy show an increased incidence of autoantibodies inducing apoptosis and/or adhesion molecule expression in EC. The involved antibodies do not necessarily belong to the group of AECAs, but AECAs appear to have enhancing potentials. Which antibodies other than AECAs are involved, and what the precise pathogenic mechanisms are of AECAs and non-AECAs in vasculopathy needs further elucidation.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.