| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
To understand pathophysiology of systemic vasculitis, it would be critical to identify and characterize autoantigens (autoAgs) for the anti-endothelial cell antibody(AECA), which are detected frequently in vasculitis. For this aim, we used proteomics approaches. Specifically, we separated proteins extracted from human umbilical vein endothelial cells(HUVEC) and Hela cells as a reference respectively by 2-dimentional electrophoresis(2DE). We then detected HUVEC-specific proteins which were recognized by serum samples from patients with systemic vasculitis by western blotting(WB). Further, we identified the candidate autoAgs for AECA by peptide mass fingerprinting and the MS/MS analysis. Preparing recombinant proteins for the identified autoAgs, we investigated their clinical significance. As a result, we detected 50 candidate autoAgs for AECA. One of the identified autoAgs was peroxiredoxin II(Prx II). The autoantibodies (autoAbs) to Prx II were detected in 68% of the tested patients with vasculitis, 7.3% in tested patients with collagen diseases but no appearent vasculitis, and 4.0% in healthy controls. Clinically, presence of the autoAbs to Prx II was linked to the elevated levels of the thrombin-antithrombin complex(TAT) and D-dimer. In addition, Prx II was detected on the surface of HUVEC. Further, the autoAbs to Prx II were frequently detected in large-size vasculitis like aortitis syndrome. Taken, together, we demonstrated by the proteomic approach that Prx II is one of the targets of AECA. The autoAb to Prx II, detected predominantly in diseases with vasculitis, would be a new marker for presence of vasculitis.
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