Antiphospholipid antibody‐dependent C5b‐9 formation

Abstract

The relationship between the presence of antiphospholipid antibodies (APA) and the production of the terminal membrane attack complex (MAC) of complement (C5b‐9) was studied. Serum samples from known high positive APA patients induced platelet activation and destruction which was inhibited by heat‐inactivation of the sera. The response was restored if the heat‐inactivated APA‐positive sera were supplemented with normal sera. Adsorption of the APA‐positive sera with phospholipid (PL)‐coated polystyrene beads inhibited platelet destruction. Addition of monoclonal antibody (mAb) to C5b‐9 (aE11) also inhibited platelet destruction, suggesting that the APA‐dependent platelet destruction might be complement‐mediated. Purified APA, in the presence of normal serum, induced C5b‐9 formation and binding to PL‐coated beads in a dose‐dependent manner as detected by flow cytometry. Prospective analysis of 200 serum samples for C5b‐9 production showed that all sera testing negative for the presence of APA also tested negative for C5b‐9 production. All sera with high levels of IgG binding to PL (GPL) showed evidence of C5b‐9 production. Sera with low or moderate GPL values showed varying levels of C5b‐9 production. These data suggest that complement may play a key role in APA‐dependent platelet activation, in vivo.

Antiphospholipid syndrome: laboratory detection, mechanisms of action and treatment

“…It was shown in mouse models that the inhibitory effect of heparin on aPL-induced foetal loss was because of inhibition of the complement system and not because of inhibition of thrombin formation [53][54][55]. Additional experiments with deficient mice have linked C3, C5 and the membrane attack complex to foetal loss and thrombosis, probably by increasing tissue factor expression on different cells [56].…”

Role of complement in antiphospholipid antibody-mediated thrombosis

“…Complement C4d bound to platelets is found in 18% of lupus patients but is highly associated with the lupus anticoagulant (50%, P < 0.0001) and aCL (P < 0.05), perhaps representing an important cellular target of aPL-mediated damage [8]. This finding is of interest, because earlier research showed that serum from patients with high-titer aPL could induce platelet activation and destruction, and this activity was destroyed by heat inactivation or the addition of monoclonal antibodies to C5b-9 [9].…”

What causes the antiphospholipid syndrome?

“…Antiphospholipid antibodies are known to bind to platelet membrane structures [14,[28][29][30][31][32], which may result in thrombocytopenia or hemostatic activation [14]. In addition, an association between aPL antibodies and immunemediated thrombocytopenia (ITP) has been established [28].…”