Studies on thrombophilic diathesis and development of a novel molecular-targeting therapy in antiphospholipid syndrome

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IgG fraction of patients with systemic lupus erythematosus (SLE) who had anti-β2-glycoprotein I (β2-GPI) antibodies induced expression of inflammatory cytokines such as IL-1β and TNFα, and tissue factor with procoagulant activity on peripheral blood mononuclear cells from healthy volunteers. On vascular endothelial cells, IL-1β and TNFα induced CX3CL1 which in turn increased platelet adhesive activity to collagen, and CCL5 which induced platelet aggregation. Expression of these cytokines, chemokines and tissue factor was all suppressed by a novel NF-κB inhibitor DHMEQ. In addition, a mouse model of antiphospholipid syndrome (APS) was established in which prothrombotic status was induced by injection of anti-β2-GPI antibodies form patients or newly made monoclonal anti-β2-GPI antibody. The monoclonal antibody showed cross-reactivity with double-stranded(ds)DNA, suggesting the common mechanism playing a role in pathogenesis of SLE and APS.