Anticoagulant activity of beta 2-glycoprotein I is potentiated by a distinct subgroup of anticardiolipin antibodies.
Plasmas of 16 patients positive for both IgG anticardiolipin (aCL) antibodies and lupus anticoagulant (LA) antibodies were subjected to adsorption with liposomes containing cardiolipin. In 5 of these plasmas both the anticardiolipin and the anticoagulant activities were co-sedimented with the liposomes in a dose-dependent manner, whereas in the remaining cases only the anticardiolipin activity could be removed by the liposomes, leaving the anticoagulant activity (LA) in the supernatant plasma. aCL antibodies purified from the first 5 plasmas were defined as aCL-type A, while the term aCL-type B was used for antibodies in the other 11 plasmas, from which 2 were selected for this study. Prolongation of the dRVVT was produced by affinity-purified aCL-type A antibodies in plasma of human as well as animal (bovine, rat and goat) origin. aCL-type B antibodies were found to be devoid of anticoagulant activity, while the corresponding supernatants containing LA IgG produced prolongation of the dRVVT only in human plasma. These anticoagulant activities of aCL-type A and of LA IgG's were subsequently evaluated in human plasma depleted of beta 2-glycoprotein I (beta 2-GPI), a protein which was previously shown to be essential in the binding of aCL antibodies to anionic phospholipids. Prolongation of the dRVVT by aCL-type A antibodies was abolished using beta 2-GPI deficient plasma, but could be restored upon addition of beta 2-GPI. In contrast, LA IgG caused prolongation of the dRVVT irrespective of the presence or absence of beta 2-GPI.(ABSTRACT TRUNCATED AT 250 WORDS)
Galli
M
M
Department of Biochemistry, University of Limburg, The Netherlands.
Comfurius
P
P
Barbui
T
T
Zwaal
R F
RF
Bevers
E M
EM
D000328:Adult; D000368:Aged; D017153:Antibodies, Anticardiolipin / Q000276:immunology*; D000925:Anticoagulants / Q000276:immunology / Q000494:pharmacology*; D001323:Autoantibodies; D001777:Blood Coagulation / Q000276:immunology; D002308:Cardiolipins; D005260:Female; D006023:Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013045:Species Specificity; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D000925:Anticoagulants; D001323:Autoantibodies; D002308:Cardiolipins; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I