IgG Antiendothelial Cell Autoantibodies from Scleroderma Patients Induce Leukocyte Adhesion to Human Vascular Endothelial Cells In Vitro Induction of Adhesion Molecule Expression and Involvement of Endothelium-derived Cytokines

IgG autoantibodies that bind human endothelial cells (AECA) were detected by ELISA in 30 of 42 samples of sera from pa-tients with scleroderma. Pretreatment of human umbilical vein endothelial cells with AECA-positive scleroderma sera, or IgG purified from these sera, led to a dose- and time-dependent increase in the ability of the cells to bind human U937 monocytic cells. Threshold-active IgG concentrations were 1–10 m g/ml; effects were significant after 3 h and max-imal after 6–12 h. IgG from AECA-negative sera or normal sera were without effect. Increased adhesion of U937 cells was accompanied by increased expression of endothelial intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Transfer of endothelial cell–con-ditioned media after pretreatment with AECA and immun-odepletion of IgG demonstrated the presence of transferable activity that mimicked the effects of AECA. Treatment with neutralizing anticytokine antibodies indicated that IL-1, generated by the endothelial cells in response to AECA, was involved in the upregulation of adhesion molecules and U937 cell adhesion. We conclude that AECA can play a pathogenic role in scleroderma by activating endothelia