Phosphatidylethanolamine induces specific conformational changes in the kininogens recognizable by antiphosphatidylethanolamine antibodies.
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.
Sugi
T
T
Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, Indianapolis 46202, USA.
Mclntyre
J A
JA
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007704:Kininogens / Q000276:immunology* / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000276:immunology*; D011487:Protein Conformation; D013927:Thrombosis / Q000097:blood / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D007704:Kininogens; D010714:Phosphatidylethanolamines