Lupus‐like anticoagulant properties of murine monoclonal antibodies to β2‐glycoprotein I

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Abstract
The lipid‐binding inhibitor of coagulation, β2‐glycoprotein I (β2GPI), has been shown to form the antigen to which some autoantibodies against anionic phospholipids (aPL) are directed. Six murine monoclonal antibodies (MAbs) of the IgG1 isotype were raised against human β2GPI and could be subdivided into three groups on the basis of mutual competition experiments. MAbs 9G1 and 8C3 (group A) markedly inhibited the binding of immunoglobulins from aPL‐positive sera to β2GPI‐coated wells. Using a lipid‐based solid‐phase radioimmunoassay, the MAbs interacted with both anionic phospholipids and phosphatidylethanolamine, but not phosphatidylcholine, in a β2GPI‐dependent manner. A cross‐reaction between β2GPI from several (including bovine) species was seen with one of the MAbs (9G1). All six MAbs induced dose‐dependent prolongation of the DAPTT, DRVVT. KCT and TTI clotting times of human plasma, whereas 9G1 was the sole antibody to be inhibitory with plasma from bovine origin. Synergistic inhibitory effects were observed with MAbs used in pairs provided that they did not compete with each other for β2GPI binding. The anticoagulant activity of the MAbs was fully neutralized by the addition of freeze‐thawed platelets. The MAbs described here resemble lupus anticoagulants in several respects which makes them valuable to study the involvement of β2GPI in the autoimmune thrombotic pathophysiology.