|Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
The presence of antiphospholipid antibodies (anticardiolipin antibodies ; aCL and lupus anticoagulants ; LA) is associated with thromboembolic manifestations, intrauterine fetal loss and thrombocytopenia. The term antiphospholipid syndrome (APS) has been used to define this set of pathologic trait, and the clinical feature of this syndrome is based on the antiphospholpid-mediated procoagulant state. In the present study, we investigated the precise characteristic of antiphospholpid antibodies, especially aCL from patients with APS and obtained following results.
1) aCL from patients with APS recognized cryptic epitope (s) appearing on the beta2-glycoprotein I (beta2-GPI) structure when beta2-GPI interacts with polyoxygenated polystirene plates as well as with lipid membranes composed of negatively-charged phospholpids such as cardiolipin and phosphatidylserine.
2) Based on the observation described above, we established a novel and accurate assay (ELISA) method for aCL using polyoxygenated polystirene plates coated with beta2-GPI,instead of CL-coated plates, and clarified the clinical significance of this system.
3) We investigated the biological significance of beta2-GPI in vitro, by using newly developed deletion mutants of beta2-GPI,and domain specific anti- beta2-GPI monoclonal antibodies.
4) We found that beta2-GPI bound to oxLDL and inhibited in vitro uptake of oxLDL by macrophages. Conversely, the binding of oxLDL was significantly increased by the simultaneous addition of human beta2-GPI and monoclonal aCL.