Anti-beta2-glycoprotein I (beta2GPI) monoclonal antibodies with lupus anticoagulant-like activity enhance the beta2GPI binding to phospholipids.

• DOI: 10.1172/jci119401
• Publication Date: 2008-02-29T17:23:39Z
• Authors: H Takeya; T Mori; E C Gabazza; K Kuroda; H Deguchi; E Matsuura; K Ichikawa; T Koike; K Suzuki
• Keywords: Lupus anticoagulant

beta2-Glycoprotein I (beta2GPI), a plasma glycoprotein with phospholipid-binding property, is known to be the actual target antigen for autoimmune type anticardiolipin antibodies (aCLs). Certain groups of aCLs (anti-beta2GPI antibodies) exert lupus anticoagulant (LA) activity and perturb function vascular endothelial cells. This investigation aimed at highlighting some insights into molecular basis by which their biological effects using anti-beta2GPI mAbs well-characterized epitopes from mice patients antiphospholipid syndrome. Anti-beta2GPI directed against third domain (Cof-20 Cof-22) fourth (Cof-21, EY1C8, EY2C9) beta2GPI inhibited thrombin generation induced Russell's viper venom in diluted that prothrombinase complex reconstituted purified clotting factors. was abrogated presence an excess amount phospholipids, thus resembling LA activity. In stark contrast, fifth carboxy-terminal region showed no LA-like These findings suggest depends on epitope specificity. Experiments carried out clarify mechanism activity, but not those without this effect, enhance binding phospholipids. addition, F(ab')2 fragment, Fab' found suggesting induce formation multiple complexes surface phospholipids because bivalent property. clustering molecules antibodies, probably multivalent property specificity, might hinder lateral mobility activation factors Clustering may also explain alter leukocytes The well-documented heterogeneous explained