New targeted therapies for treatment of thrombosis in antiphospholipid syndrome.
Antiphospholipid (aPL) antibodies (Abs) are associated with thrombosis and pregnancy loss in antiphospholipid syndrome (APS), a disorder initially characterised in patients with systemic lupus erythematosus (SLE) but now known to occur in the absence of other autoimmune disease. There is strong evidence that aPL Abs are pathogenic in vivo, from studies of animal models of thrombosis, endothelial cell activation and pregnancy loss. In recent years, progress has been made in characterising the molecular basis of this pathogenicity, which includes direct effects on platelets, endothelial cells and monocytes as well as activation of complement. This review summarises the clinical manifestations of APS and current modalities of treatment, and explains recent advances in understanding the molecular events triggered by aPL Abs on target cells in coagulation pathways as well as effects of aPL Abs on complement activation. Based on this information and on additional scientific evidence using in vitro and in vivo models, new potential targeted therapies for treatment and/or prevention of thrombosis in APS are proposed and discussed.
Pierangeli
Silvia S
SS
Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-1165, USA. sspieran@utmb.edu
Vega-Ostertag
Mariano E
ME
González
Emilio B
EB
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000097:blood* / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001792:Blood Platelets / Q000276:immunology / Q000502:physiology; D003167:Complement Activation; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D009000:Monocytes / Q000502:physiology; D011516:Prothrombin / Q000276:immunology / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000097:blood
D017152:Antibodies, Antiphospholipid; D053482:beta 2-Glycoprotein I; D011516:Prothrombin