Complement and the antiphospholipid syndrome

Abstract

The antiphospholipid antibody syndrome (APS) is characterized by arterial or venous thrombosis or pregnancy morbidity in patients with persistent antiphospholipid antibodies (aPL). Experimental data supporting activation of the complement cascade has provided critical insight into the underlying pathophysiology of aPL-induced pregnancy loss and thrombosis. Although the mechanism by which pregnancy loss and thrombosis is incompletely elucidated, studies using mice deficient in complement components and specific inhibitors to complement have demonstrated that activation of complement contributes to fetal loss, growth restriction and thrombosis. Inhibition of complement activation can prevent these complications. Use of a specific complement inhibitor to C5 has been used successfully in a patient with catastrophic APS undergoing renal transplantation. Activation of complement plays an important role in the pathogenesis of aPL-induced pregnancy morbidity and thrombosis. This understanding has been advanced primarily using mouse models of APS and clinical studies in patients with APS are needed. Although there is currently no specific complement-targeted therapy approved for APS, developing and evaluating complement-targeted therapies in patients with APS are warranted. Complement inhibition may provide a novel upstream treatment option for patients with APS compared with the current standard treatment of anticoagulation.