Antiphospholipid syndrome (APS) is an acquired
autoimmune disease characterized by thromboembolic events, pregnancy morbidity, and the presence of antiphospholipid (aPL)
antibodies. There is sound evidence that aPL act as pathogenic
autoantibodies being responsible for vascular clots and
miscarriages. However, the exact mechanisms involved in the clinical manifestations of the syndrome are still a matter of investigation. In particular, while vascular
thrombosis is apparently not associated with
inflammation, the pathogenesis of
miscarriages can be explained only in part by the aPL-mediated hypercoagulable state and additional non-thrombotic effects, including placental
inflammation, have been described. Despite this difference, evidence obtained from animal models and studies in APS patients support the conclusion that complement activation is a common denominator in both vascular and obstetric APS. Tissue-bound aPL rather than circulating aPL-beta2
glycoprotein I
immune complexes seem to be responsible for the activation of the classical and the alternative
complement pathways. The critical role of
complement is supported by the finding that
complement-deficient animals are protected from the pathogenic effect of passively infused aPL and similar results have been obtained blocking complement activation. Moreover, elevated levels of complement activation products in the absence of abnormalities in regulatory molecules have been found in the plasma of APS patients, strongly suggesting that the activation of
complement cascade is the result of aPL binding to the target
antigen rather than of a defective regulation. Placental
complement deposits represent a further marker of complement activation both in animals and in patients, and there is also some suggestive evidence that complement activation products are deposited in the affected vessels. The aim of this review is to analyze the state of the art of
complement involvement in the pathogenesis of APS in order to provide insights into the role of this system as predictive
biomarker for the clinical manifestations and as therapeutic target.