Anti-endothelial cell antibodies (AECA) have been frequently detected in 
systemic vasculitis, which affects blood vessels of various sizes. To understand 
the pathogenic roles of AECA in systemic vasculitis, we attempted to identify 
target antigens for AECA comprehensively by a proteomic approach. Proteins 
extracted from human umbilical vein endothelial cells (HUVEC) were separated by 
two-dimensional electrophoresis, and Western blotting was subsequently conducted 
using sera from patients with systemic vasculitis. As a result, 53 autoantigenic 
protein spots for AECA were detected, nine of which were identified by mass 
spectrometry. One of the identified proteins was peroxiredoxin 2 (Prx2), an 
anti-oxidant enzyme. Frequency of anti-Prx2 autoantibodies, measured by 
enzyme-linked immunosorbent assay (ELISA), was significantly higher in systemic 
vasculitis (60%) compared to those in collagen diseases without clinical 
vasculitis (7%, P < 0·01) and healthy individuals (0%, P < 0·01). Further, the 
titres changed in parallel with the disease activity during time-courses. The 
presence of anti-Prx2 autoantibodies correlated significantly with elevation of 
serum d-dimers and thrombin-antithrombin complex (P < 0·05). Immunocytochemical 
analysis revealed that live endothelial cells expressed Prx2 on their surface. 
Interestingly, stimulation of HUVEC with rabbit anti-Prx2 antibodies increased 
secretion of interleukin (IL)-6, IL-1β, IL-1ra, growth regulated oncogene 
(GRO)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage 
colony-stimulating factor (GM-CSF), IL-8 and monocyte chemoattractant protein 
(MCP)-1 more than twofold compared to that of with rabbit immunoglobulin (Ig)G. 
Taken together, our data suggest that anti-Prx2 autoantibodies would be a useful 
marker for systemic vasculitis and would be involved in the inflammatory 
processes of systemic vasculitis.