Autoantibody Target of Vascular Disease Identified

Plasminogen antibodies affect clot lysis

FRIDAY, Aug. 15 (HealthDay News) -- Many patients with an autoimmune inflammatory vascular disease have antibodies against plasminogen, which reduces its conversion to plasmin and delays clot lysis, according to research published online Aug. 13 in the Journal of the American Society of Nephrology.

David J. Bautz and colleagues from the University of North Carolina in Chapel Hill used plasmapheresis material from patients with inflammatory vascular disease caused by anti-neutrophil cytoplasmic autoantibodies (ANCA) to identify antigens targeted by antibodies against complementary proteinase 3 (cPR3105-201), a recombinant protein translated from the antisense strand of the PR3 autoantigen gene.

The researchers found that plasminogen was a target of the antibodies, and reactivity was lost in two patients when plasminogen was converted to plasmin. The antibodies decreased the conversion of plasminogen to plasmin and delayed the lysis of fibrin clots. In five patients, the antibodies targeted a surface-exposed loop structure within the plasminogen protease domain, the report indicates. Serum levels of anti-plasminogen antibodies were significantly higher in 72 PR3-ANCA patients compared with healthy controls and patients with other diseases. Five of nine PR3-ANCA patients with documented deep venous thrombosis were also positive for anti-plasminogen antibodies, the authors report.

"In summary, capitalizing on interactions with complementary proteins, specifically complementary PR3, this study identified plasminogen as a previously undescribed autoantigen in PR3-ANCA vasculitis," Bautz and colleagues conclude.

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