ANTIVASCULAR ENDOTHELIAL-CELL ANTIBODIES (AECA) - COMPARISON OF 2 ASSAY-METHODS AND CLINICAL-APPLICATIONS

Vascular endothelial cells may be a target for autoantibodies (AECAs) against membrane antigens that are constitutively expressed, induced o r bound to their surface, To test this hypothesis, we used an enzyme-l inked immunosorbent assay (ELISA) with two types of human endothelial cells as the substrate, i.e., human umbilical cord vein endothelial ce lls (HUVECs) or the hybrid cell line EAhy-926 obtained by fusion of HU VECs with the bronchial carcinoma cell line A549, A comparative functi onal study of these two cell types demonstrated that EAhy-926 cells pr oduced only small amounts of VIII von Willebrand factor and tissular f actor, did not contain Weibel Palade bodies visible under the electron microscope, and expressed ICAM-1 and selectin E in levels of no more than 15% of those expressed by human umbilical cord vein endothelial c ells both after stimulation by bacterial lipopolysaccharide and under basal conditions, However, the two assay methods yielded similar IgG A ECA titers when used on sera from patients with rheumatoid vasculitis or antiphospholipid syndrome, These antibodies did not exhibit cytotox icity for cord vein or EAhy-926 cells, They were not specific for endo thelium, since their activity decreased by a mean of 40% after incubat ion of sera with the epithelial cell line A549, A cross-sectional stud y of 565 sera demonstrated that anti-vascular IgG and IgM AECAs reacti ve with EAhy-926 cells occurred mainly in patients with dermatomyositi s (IgG, 58%; IgM, 22%), systemic scleroderma (IgG, 48%; IgM, 18%), pri mary Sjogren's syndrome (IgG, 44%; IgM, 12%) and secondary and primary systemic vasculitides (IgG, 38%; IgM, 18%) including Wegener's granul omatosis. A longitudinal study in patients with Wegener's granulomatos is showed that AECAS were predictive of disease activity.