Summary
Autoantibodies to the zwitterionic phospholipid (PL), phosphatidylethanolamine (PE)
have been described in patients with thrombotic diseases. Recently, we reported that
many antiphosphatidylethanolamine antibodies (aPE) are not specific for PE per se,
but are directed to plasma proteins which can bind PE, for example, high molecular
weight kininogen (HK), low molecular weight kininogen (LK) and/or proteins in complex
with HK, factor XI or prekallikrein. In the ELISA, we now show that intact HK binds
to all PL tested. By using a monoclonal antibody (mAb) to the HK light chain, binding
to cardiolipin (CL) was highest followed by phosphatidylserine (PS), PE and phosphatidylcholine
(PC). By contrast, LK bound best to PE, with lesser amounts binding to PC and CL.
Many aPE recognize only a kininogen-PE complex and neither PE nor kininogen when they
are tested independently. We now report that these aPE are specific for the kininogen-PE
complex as they do not recognize the kininogens when the latter are presented on other
PL substrates. This indicates that PE induces unique antigenic conformational changes
in the kininogens which are not induced when the kininogens bind to other PL. The
kininogens bind to platelets and endothelial cells through an as yet undefined receptor.
Since PE is a normal constituent of the outer layer of cell and platelet plasma membranes,
it is available for the kininogens to bind. In vitro studies showed that purified
IgG which bound kininogen-PE complexes in ELISA also caused platelets to undergo irreversible
aggregation when stimulated by subthreshold concentrations of bovine thrombin.
