Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation

β2-glycoprotein I (apolipoprotein H)

H. P. McNeil, R. J. Simpson, C. N. Chesterman, S. A. Krilis*

*Corresponding author for this work

Research output: Contribution to journalArticle

1566 Citations (Scopus)

Abstract

Anti-phospholipid (aPL) antibodies that exhibit binding in cardiolipin (CL) ELISA can be purified to >95% purity by sequential phospholipid affinity and ion-exchange chromatography. However, these highly purified aPL antibodies do not bind to the CL antigen when assayed by a modified CL ELISA in which the blocking agent does not contain bovine serum, nor do they bind to phospholipid affinity columns. Binding to the phospholipid antigen will only occur if normal human plasma, human serum, or bovine serum is present, suggesting that the binding of aPL antibodies to CL requires the presence of a plasma/serum cofactor. Using sequential phospholipid affinity, gel-filtration, and ion-exchange chromatography, we have purified this cofactor to homogeneity and shown that the binding of aPL antibodies to CL requires the presence of this cofactor in a dose-dependent manner. N-terminal region sequence analysis of the molecule has identified the cofactor as β2-glycoprotein (β2GPI) (apolipoprotein H), a plasma protein known to bind to anionic phospholipids. These findings indicate that the presence of β2GPI is an absoute requirement for antibody-phospholipid interaction, suggesting that bound β2GPI forms the antigen to which aPL antibodies are directed. Recent evidence indicates that β2GPI exerts multiple inhibitory effects on the coagulation pathway and platelet aggregation. Interference with the function of β2GPI by aPL antibodies could explain the thrombotic diathesis seen in association with these antibodies.

Original languageEnglish
Pages (from-to)4120-4124
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number11
DOIs
Publication statusPublished - 1990
Externally publishedYes

Keywords

  • anti-cardiolipin antibodies
  • lipid-protein complex
  • thrombosis

Fingerprint Dive into the research topics of 'Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β<sub>2</sub>-glycoprotein I (apolipoprotein H)'. Together they form a unique fingerprint.

  • Cite this