Antiendothelial cell activity in systemic diseases

First detected by fluorescence analysis, the specificity of antibody binding to endothelial cell (EC) has long been established, and a quantitative cellular enzyme-linked immunosorbent assay (ELISA) developed, with human umbilical vein EC (HUVEC) as the substrate. Anti-EC antibodies (AECA) were subsequently described in a number of systemic diseases. However, a consensus on the prevalence of AECA has not yet been reached. The proportion of AECA-positive sera ranges from 16 to 63% in systemic lupus erythematosus (SLE), from 0 to 87% in rheumatoid arthritis, and from 45 to 77% in mixed connective tissue disease. Interestingly, type IV nephritis is present in 100% of SLE patients with AECA. A total of 167 disease-associated sera from 79 patients with large- or medium-sized (group I) and 88 with small-sized vessel vasculitis (group II) were examined for the presence of AECA using the cellular ELISA with permanent EA.hy926 cell line cells as the substrate. These were evaluated before and after incubation with epithelial cells. EC plus epithelial cell (cC) extracts were fractionated and blotted. The binding of antibodies to cC was observed in group II, but not in group I sera. Eight antigenic proteins appeared to be specific for EC, whereas three were shared with cC. Hence, EC-specific activity is more often encountered in group I than in group II patients. Prompted by the widespread awareness of the limitations of the tests currently in use, we established seven clones of EC, in the hope that each of them would express disease-specific membrane autoantigens. This panel is meant to distinguish reactivities of AECA. In addition, antiphospholipid antibodies might partly account for anti-EC reactivity.