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Antiphospholipid Antibodies in Implantation Failures*

Authors

  • J. A. McIntyre

    1. HLA-Vascular Biology Laboratory, St Francis Hospital and Health Centers and Indiana/Purdue Universities at Indianapolis, Indianapolis, IN 46107, USA
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  • *

    Presented lecture at the June 2002 annual meeting of the American Society for Reproductive immunology.

Address reprint requests to John A. McIntyre, HLA-Vascular Biology Laboratory, St Francis Hospital & Health Centers, 1500 Albany Street, #1109, Beech Grove, IN 46107, USA. E-mail: john.mcintyre@ssfhs.org

Abstract

PROBLEM:  The amino phospholipids (PL), phosphatidylserine (PS) and phosphatidylethanolamine (PE) are distributed asymmetrically in the plasma membranes of eucaryotic cells. This arrangement involves active transport of PS and PE from the outer to inner membrane leaflet by an aminophospholipid translocase (flipase). Cell activation, injury and programmed cell death (apoptosis) cause collapse of the PS/PE asymmetry by activation of another enzyme system, scramblase. Unlike other cells, the developing trophoblast exteriorizes PS during its differentiation.

METHODS OF STUDY:  An analysis of published and unpublished data.

RESULTS:  The trophoblast is targeted by antiphospholipid antibodies (aPL), especially to PS (aPS). Cardiolipin is not present in the trophoblast plasma membrane, nonetheless, anticardiolipin (aCL) has been implicated in trophoblast pathology. The aPS and aCL are often crossreactive. Both animal and in vitro experimental models have shown monoclonal and polyclonal aPS and aCL to specifically destroy trophoblast, inhibit syncytium formation, halt human chorionic gonadatropin (hCG) production, and limit trophoblast invasion. Antibodies to PE (aPE) have not been well characterized, however, recent reports from several independent laboratories document that aPE are associated significantly with very early (embryonic) recurrent pregnancy loss (RPL). Umeda and coworkers have shown that during cytokinesis (late telophase) of Chinese hamster ovary (CHO) cells, formation of PE rafts in cleavage furrows is required for completion of cell division and formation of daughter cells. This raises the question whether aPE might interfere with implantation and cell division during embryogenesis.

CONCLUSIONS:  A role for aPL in implantation failure and occult pregnancy loss constitutes the basis of this overview.

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