title: Highly increased plasma concentrations of the nicked form of beta(2) glycoprotein I in patients with leukemia and with lupus anticoagulant: measurement with a monoclonal antibody specific for a nicked form of domain V.
abstract: beta(2)-Glycoprotein I (beta(2)GPI) consists of five tandem repeated domains (I, II, III, IV, and V). The nicked form of beta(2)GPI (N-beta(2)GPI ) which was cleaved by plasmin in vitro at Lys 317-Thr 318 in domain V, showed reduced affinity for the negatively charged phospholipids, especially cardiolipin (CL). Recently, the N-beta(2)GPI was detected in the plasma of patients with disseminated intravascular coagulation syndrome (DIC) by an immunological method. In the present study, we prepared monoclonal antibodies for the nicked form, and demonstrated that the concentrations of this form of beta(2)GPI, which were analyzed by a sandwich ELISA using two specially prepared monoclonal antibodies, were significantly increased in the plasma of patients with leukemia (n = 51, mean +/- SD: 162.0 +/- 118.3 ng/ml) and with lupus anticoagulant (LA) (n =40, mean +/- SD: 3,041.5 +/- 16,579.7 ng/ml), compared to the normals (n = 33, mean +/- SD: 1.04 +/- 1.54 ng/ml). We found a significant correlation between the concentrations of N-beta(2)GPI and those of typical molecular markers for a fibrinolytic state such as plasmin-alpha(2) plasmin inhibitor complex (PIC) and D-dimer in patients with leukemia, but not in patients with LA. These results suggested that the generation of N-beta(2)GPI was caused by plasmin in the patients with leukemia, and by unknown proteases in the patients with LA. In the patients with LA, the levels of N-beta(2)GPI tended to be higher in those without thrombosis than in those with thrombosis.
authors.affiliation: Narita R&D Center, Iatron Laboratories Inc., Mito, Takomachi, Katori-Gun, Chiba 289-2247, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Itoh
authors.forename: K
authors.initials: K
authors.lastname: Inuzuka
authors.forename: I
authors.initials: I
authors.lastname: Kohno
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: H
authors.initials: H
authors.lastname: Shiku
authors.forename: N
authors.initials: N
authors.lastname: Ohkura
authors.forename: H
authors.initials: H
authors.lastname: Kato
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D002846:Chromatography, Affinity / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000097:blood* / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007938:Leukemia / Q000097:blood*; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D053482:beta 2-Glycoprotein I
chemical_list: D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D016682:Lupus Coagulation Inhibitor; D053482:beta 2-Glycoprotein I