Antiendothelial cell antibodies in lupus: correlations with renal injury and circulating markers of endothelial damage

Abstract

Systemic lupus erythematosus is characterized by the production of a broad spectrum of autoantibodies. Autoantibodies directed against endothelial cells (AECA) have been particularly well documented. We investigated associations between such antibodies, double-stranded DNA (dsDNAb), phospholipid (cardiolipin, ACA), and indices of activity and chronicity scored on renal biopsy specimens from 22 patients with acute lupus. AECA were present in 73% of these patients, and both the percentage of patients with AECA and the mean antibody titre fell significantly as patients entered remission. When patients already on immunosuppressive therapy were excluded from analysis (n = 7), only levels of AECA and DNAb (p = 0.02) correlated with histological evidence of active lesions and the presence of glomerular epithelial cell crescents; no correlation was found with chronic changes in the renal biopsies. Serum von Willebrand factor (vWf) and serum total protein S levels, two parameters reflecting endothelial cell function, were also measured during acute disease and remission. vWf concentrations were elevated during acute disease (m = 1.9 IU/ml, p = 0.02), but the values did not correlate with AECA titres. In contrast, total protein S levels were reduced (0.81 IU/ml vs. 0.97 IU/ml, p = 0.01) during active disease, but remained within the normal range (0.56-1.16 IU/ml). Furthermore, protein S levels were inversely related to levels of AECA (r = -0.4, p = 0.01). AECA were therefore present in most patients with acute lupus nephritis and were associated with histological evidence of active renal injury and serological evidence of endothelial cell dysfunction. These data provide indirect support for a pathogenic role for AECA in lupus nephritis.