Antiphospholipid antibody-dependent C5b-9 formation.
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.
Stewart
M W
MW
Department of Laboratory Medicine and Pathology, University of Alberta Hospitals, Edmonton, Canada.
Etches
W S
WS
Gordon
P A
PA
D000255:Adenosine Triphosphate / Q000378:metabolism; D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000378:metabolism; D003182:Complement C5 / Q000378:metabolism*; D050776:Complement C5b; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology*
D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D003182:Complement C5; D015938:Complement Membrane Attack Complex; D007074:Immunoglobulin G; D050776:Complement C5b; D000255:Adenosine Triphosphate