Apoptosis and the antiphospholipid syndrome.
The target of many antiphospholipid autoantibodies (APA) has been shown to be a complex between anionic phospholipid (PL) and the plasma protein beta 2-glycoprotein I (beta 2-GPI), but the identity of the natural target(s) and/or immunogen for APA in vivo remains undetermined. The anionic PL of cell membranes represent important potential targets and immunogenes for APA. Although anionic PL are normally absent from the extracellular surface of cell membranes, they redistribute from the inner to the outer leaflet during apoptosis. We and others have shown that beta 2-GPI binds selectively to the surface of apoptotic, but not viable, cells, and that the binding of beta 2-GPI to the surface of apoptotic cells generates an epitope recognized by APA from patients with both primary antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). In this review, we discuss recent findings, which suggest not only that apoptotic cell-bound beta 2-GPI is injected by non-intravenous routes. We also review briefly the potential role of oxidation in generating epitopes responsible for the recognition and induction of APA. Taken together, we believe that the available evidence supports a role for apoptotic cells as far as targets of APA and possible players in the induction of APA.
Rauch
J
J
Division of Rheumatology, Department of Medicine, The Montreal General Hospital Research Institute, McGill University, Montreal, Quebec, H3G 1A4, Canada. mdrh@musica.mcgill.ca
Subang
R
R
D'Agnillo
P
P
Koh
J S
JS
Levine
J S
JS
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000096:biosynthesis; D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000473:pathology*; D017209:Apoptosis / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D006801:Humans; D008563:Membrane Lipids / Q000502:physiology; D010743:Phospholipids / Q000502:physiology
D017152:Antibodies, Antiphospholipid; D008563:Membrane Lipids; D010743:Phospholipids