Presence of circulating antibodies to a disease-specific antigen on cultured human dermal microvascular endothelial cells in patients with Behcet's disease

Behcet's disease is a chronic, multisystem disorder characterized by a recu rrent inflammatory reaction. Antiendothelial cell antibodies have been dete cted in the serum from patients with autoimmune diseases with presenting va sculitis and it is assumed that they can induce damage to the endothelial c ells, In this study, me detected antiendothelial cell antibodies in the ser um from patients with Behcet"s disease using an enzyme-linked immunosorbent assay, electrophoresis and immunoblotting. The cytolysis of human dermal m icrovascular endothelial cells (HDMEC) was measured using a cytotoxicity as say, The serum from 37.4% of Behcet's disease patients showed IgM antibodie s against unstimulated HDMEC while the serum from 18.4% of patients showed an increase in IgM antibody titer after IFN-gamma pretreatment, The frequen cy of vasculitis was higher in the IgM-positive Behcet"s disease patients t han in the IgM-negative patients, In Western blotting, IgM-positive Behcet' s disease serum reacted With the 44 kDa HDMEC surface antigen, whereas IgM- positive systemic lupus erythematosus serum reacted with the 81 kDa HDMEC s urface antigen. The reactivity to the 44 kDa protein band was also observed in cultured human umbilical vein endothelial cells but not in fibroblasts, A431 cells or SK-MEL-2 cells. Serum from Behcet's disease patients incubat ed with human complement or mononuclear cells produced no significant lysis of HDMEC, and cultured HDMEC were resistant to antibody-dependent cell-med iated cytotoxicity, The results suggest that antibodies against antigens on the surface of endothelial cells may play a role in inducing vasculitis in Behcet's disease, not through a direct toxic effect of an antiendothelial cell antibody but by an indirect effect involving the activation of endothe lial cells to produce cytokines.