Fig. 4.

Proposed mechanism for the pathogenic effects of aPL antibodies on tissue injury. APL antibodies are preferentially targeted to the placenta where they activate complement via the classical pathway. The complement cascade is initiated; C3 and subsequently C5 are activated. C5a is generated and attracts and activates neutrophils, monocytes and platelets, and stimulates the release of inflammatory mediators, including reactive oxidants, proteolytic enzymes, chemokines, cytokines and complement factors. Complement activation is amplified by the alternative pathway. This results in further influx of inflammatory cells and ultimately fetal injury. Depending on the extent of damage, either death in utero or fetal growth restriction ensues. (PMN, neutrophil; Mφ, monocyte-macrophage) From Girardi et al., Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest 2003; 112:1644–1654. Republished with permission.