ARE IMMUNOGLOBULINS WITH LUPUS ANTICOAGULANT ACTIVITY SPECIFIC FOR PHOSPHOLIPIDS

Recent studies have suggested that the lupus anticoagulant (LA) may be specific for prothrombin, prothrombin-phospholipid complexes, or beta 2 glycoprotein 1 (beta2GP1) rather than phospholipids. We performed a series of experiments to determine whether LA is indeed phospholipid s pecific. IgG was purified from sera of six patients with the antiphosp holipid syndrome (APS) and 10 healthy controls. The six IgG-APS prepar ations had both LA and anticardiolipin (aCL) activity. Incubation of t he six IgG-APS preparations with cardiolipin (CL), phosphatidylserine (PS), phosphatidylcholine (PC), or PS/PC (20:80) liposomes in Tris-buf fered saline, resulted in loss of LA activity from the supernatant. We postulated that loss of activity might have resulted from absorption of IgG LA antibodies by phospholipids, a dilutional effect, or the pre sence of phospholipids in the supernatant causing 'by-pass' of IgG LA inhibitory activity. To distinguish between these possibilities, we re -isolated IgG from the supernatants and re-tested them for LA activity . IgG re-isolated from the PS, CL and PS/PC supernatants had no LA act ivity, but LA activity remained in the PC supernatant. This suggested that IgG with LA activity was absorbed by negatively charged but not b y zwitterionic phospholipids. In like manner, PS, CL and PS/PC, but no t PC liposomes, absorbed IgG with aCL activity. Mixtures of the phosph olipid liposomes with beta2GP1 did not modify the absorption of IgG wi th LA or aCL activity. Finally, we demonstrated that IgG eluted from i mmunoglobulin-cardiolipin liposome complexes had LA activity. Based on these findings, we conclude that at least one population of antibodie s with LA activity is phospholipid specific.