BACKGROUND: Antiendothelial cell
antibodies (AECA), usually detected using human
umbilical vein endothelial cells (HUVEC), are frequently observed in systemic
vasculitis, but their
pathogenic role is unclear.
Heterogeneity of
endothelial cells necessitates use of clinically relevant
endothelial cells for elucidation of the role of AECA in systemic
vasculitis involving small
blood vessels of specific
organs. METHODS: Human
endothelial cells were isolated from normal tissue specimens from the nose,
kidney,
lung,
liver, and
umbilical vein. Using
flow cytometry, AECA were detected against both unstimulated and cytokine-stimulated [
tumor necrosis factor-alpha (
TNF-alpha) and
interferon-gamma (
IFN-gamma)]
endothelial cells. Functional capacity of AECA was determined by complement fixation
assay. Sera from patients with
Wegener's granulomatosis (16), limited
Wegener's granulomatosis (8),
renal limited disease (4),
microscopic polyangiitis (MPA) (5),
rheumatoid arthritis (10), and
systemic lupus erythematosus (SLE) (9), and from healthy controls (20) were analyzed. RESULTS: Compared with controls (1)
Wegener's granulomatosis is significantly associated with noncytotoxic AECA that selectively bind surface
antigens on unstimulated nasal,
kidney, and
lung endothelial cells; (2) binding of
Wegener's granulomatosis AECA to
kidney and nasal
endothelial cells in particular was lost upon treatment with
IFN-gamma and
TNF-alpha; (3) the two
cytokines per se were
cytotoxic (30%) to nasal and
lung endothelial cells and
lysis was further increased (60%) by addition of systemic
vasculitis serum; and (4)
Wegener's granulomatosis serum caused agglutination of cytokine-stimulated nasal
endothelial cells. CONCLUSION: Based on these findings we suggest that AECA may be one factor involved in the initiation of
Wegener's granulomatosis.
Antigen identification and elucidation of the
pathogenic roles of AECA and
inflammatory cytokines in systemic
vasculitis using these cells will be particularly important.
