Up‐regulation of the endothelial cell adhesion molecule intercellular adhesion molecule‐1 (ICAM‐1) by autoantibodies in autoimmune vasculitis

Autoimmune vasculitis is characterized by the presence of autoantibodies, particularly anti‐neutrophil cytoplasmic antibodies (ANCA) and anti‐nuclear antibodies (ANA), in patient sera. These autoantibodies have an incompletely understood role in development of vascular injury. The expression or up‐regulation of cell adhesion molecules is an early phase in the development of an inflammatory vascular lesion. Autoantibody‐positive sera from patients with vasculitis were assessed for their ability to modulate adhesion molecule expression by human umbilical vein endothelial cells (HUVEC). Autoantibody‐positive serum samples from 11 out of 21 patients with primary vasculitis produced substantial up‐regulation of ICAM‐1 on HUVEC. Autoantibody‐negative samples did not produce adhesion molecule up‐regulation. Up‐regulation of adhesion molecules on HUVEC was observed with samples positive for ANA, a phenomenon not previously reported. Preincubation of the sera with purified antigens recognized by ANCA failed to block this activation. In addition, MoAbs to ANCA antigens were ineffective at inducing ICAM‐1 up‐regulation, suggesting that activation is independent of the molecular specificity of the antibody. This capacity of ANCA‐ and ANA‐positive sera to up‐regulate adhesion molecules on endothelial cells may be a factor in the vessel wall inflammation seen in ANCA‐associated vasculitis.