2004 Fiscal Year Final Research Report Summary
Studies on target molecules for anti-endothelial cells autoantibodies detected in systemic vasculitis.
Project/Area Number |
15591069
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
膠原病・アレルギー・感染症内科学
|
Research Institution | St.Marianna University School of Medicine |
Principal Investigator |
KATO Tomohiro St.Marianna University School of Medicine, Institute of Medical Science, associate professor, 難病治療研究センター, 助教授 (80233807)
|
Project Period (FY) |
2003 – 2004
|
Keywords | vasculitis / autoantigens / peroxiredoxin II |
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.
|
Research Products
(14 results)