Inhibition of activated protein C and its cofactor protein S by antiphospholipid antibodies.
We have investigated the effects of purified IgG fractions from plasma containing the lupus anticoagulant (LAC) and/or IgG anticardiolipin antibody (ACA) on the degradation of factor Va by an activated protein C-protein S complex. Plasma samples from 10 patients were studied. LAC was detected by a Russell's Viper venom technique. ACA was determined by ELISA. IgG fractions were obtained from each plasma sample by protein A-Sepharose fractionation. This fraction was shown to exhibit ACA/LAC activity. Using purified activated protein C (APC), protein S and phosphatidylserine/phosphatidylcholine, factor Va degradation was assessed in the presence and absence of IgG fractions from LAC/ACA containing plasmas. After 2 min incubation the mean factor Va degradation by APC and protein S in the presence of IgG LAC/ACA fractions was 14% compared with 52% with normal IgG. A similar effect was seen when phospholipid was substituted by washed freeze-thawed platelets. Experiments employing varying concentrations of protein S and phospholipid revealed marked differences in respect of the inhibitory specificity of the different antiphospholipid antibodies. These results indicate that antiphospholipid antibodies have an inhibitory effect on the activated protein C/protein S complex and provide some explanation for a relationship between antiphospholipid antibodies and thrombosis.
Malia
R G
RG
University Department of Haematology, Royal Hallamshire Hospital, Sheffield.
Kitchen
S
S
Greaves
M
M
Preston
F E
FE
D001323:Autoantibodies / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000032:analysis / Q000276:immunology; D002308:Cardiolipins / Q000276:immunology; D015943:Factor Va / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D016682:Lupus Coagulation Inhibitor; D010743:Phospholipids / Q000276:immunology*; D011486:Protein C / Q000037:antagonists & inhibitors*; D017293:Protein S; D013927:Thrombosis / Q000276:immunology*
D001323:Autoantibodies; D001779:Blood Coagulation Factors; D002308:Cardiolipins; D006023:Glycoproteins; D007074:Immunoglobulin G; D016682:Lupus Coagulation Inhibitor; D010743:Phospholipids; D011486:Protein C; D017293:Protein S; D015943:Factor Va