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Immunological specificity and mechanism of action of IgG lupus
anticoagulants
V Pengo, P Thiagarajan, SS Shapiro and MJ Heine
Although observations have implied that lupus anticoagulants have
immunologic specificity toward anionic phospholipids, this assumption has
been directly demonstrated in only one patient with a monoclonal IgM
paraprotein. We tested the generality of this hypothesis directly by
isolating five IgG lupus anticoagulants from patients with lupuslike
syndromes and/or thrombosis. IgG lupus anticoagulant fractions were
isolated free of other plasma proteins and free of contaminating
phospholipid by adsorption to and elution from cardiolipin-cholesterol-
dicetyl phosphate liposomes, followed by chromatography on protein A-
Sepharose. Cardiolipin liposomes, but not phosphatidylcholine liposomes,
were capable of removing all, or nearly all, lupus anticoagulant activity
from patient plasma. The affinity-purified IgG preparations reacted with
cardiolipin, phosphatidylserine, phosphatidylinositol, and phosphatidic
acid, but not with phosphatidylcholine or phosphatidylethanolamine, and
inhibited calcium- dependent binding of prothrombin and of factor X to
phosphatidylserine- coated and to cardiolipin-coated surfaces. F(ab')2
fragments retained lupus anticoagulant activity and bound to cardiolipin in
an enzyme- linked immunosorbent assay (ELISA). Anticardiolipin and lupus
anticoagulant activity were both present in acidic fractions on isoelectric
focusing. These data strongly suggest that most, if not all, lupus
anticoagulants are antibodies that have immunologic specificity towards
anionic phospholipids, thereby blocking the calcium- mediated binding of
vitamin K-dependent coagulation factors to coagulation-active phospholipid
surfaces.
Volume 70,
Issue 1,
pp. 69-76,
07/01/1987
Copyright © 1987 by The American Society of Hematology
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