Characterization of autoantibodies to endothelial cells in systemic sclerosis (SSc): association with pulmonary fibrosis

To determine the prevalence and the characterization of antibodies to endot helial cells in patients with SSc, serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 20 healthy contro l subjects were examined by ELISA using cultured human umbilical vein endot helial cells (HUVEC), indirect immunofluorescence analysis (IIF), and immun oblotting using cytoplasmic extract of HUVEC. IgG and/or IgM isotype anti-e ndothelial cell antibodies (AECA) were demonstrated by ELISA in 43 of 80 pa tients with SSc (54%), in 15 of 20 patients with SLE (75%), and in none of 20 healthy control subjects. Immunofluorescence analysis on HUVEC substrate showed homogeneous cytoplasmic staining. Immunoblotting demonstrated that these patients had antibodies directed to one or several antigens of approx imately 60, 90, 110 and 140 kD, and the most common responses were to the 9 0-kD antigen. By the immunofluorescence method using HUVEC, affinity-purifi ed anti-90-kD antibodies showed identical cytoplasmic staining to that prod uced by sera positive for AECA. Furthermore, AECA were closely correlated w ith pulmonary fibrosis in patients with SSc. These findings suggest that pa tients with SSc have abnormal antibodies to endothelial cell antigens, and support the hypothesis that endothelial dysfunction is involved in the deve lopment of this disease.