Autoantibodies to endothelial cells and neutrophil cytoplasmic antigens in systemic vasculitis

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Abstract
The interaction of circulating autoantibodies with the endothelium may be an important mechanism in the pathogenesis of systemic vasculitis. In a prospective study, we looked for circulating anti-endothclial cell autoantibodies (AECA) and anti-neutrophil cytoplasm autoantibodies (ANCA) in 80 patients with suspected systemic vasculitis. AECA were measured using an isotype-specific cellular ELISA incorporating human umbilical vein endothelial cells. ANCA activity was determined by indirect immunofluorescence and radioimmunoassay. Sequential studies were performed on sera from four cases with dual positivity, where autoantibody binding was compared with von Willebrand factor (vWF) concentration and disease activity. IgG AECA were significantly higher in the 27 ANCA-positive sera as compared with normal controls (P= 0027) with IgG (P= 0 009) and IgA (P = 0046) AECA isotypes correlating with ANCA positivity; in contrast, no differences were found between AECA levels in the ANCA-negativc sera and the normal controls. Cross-inhibition studies pointed to the co-existencc of two autoantibody populations. An association between autoantibody binding, disease activity and vWF concentration was found for both ANCA and AECA. Some patients with systemic vasculitis have detectable AECA that recognize different epitopes to ANCA and like ANCA. their titre correlates with disease activity and thus they may have a pathogenetic role in these conditions.