Human monoclonal anti-phospholipid antibodies selectively bind to membranephospholipid and beta(2)-glycoprotein I (beta(2)-GPI) on apoptotic cells

The ability of an anti-phospholipid (LJ1) and an anti-beta(2)-GPI (RSP-57) human MoAb to bind to apoptotic but not viable cells was demonstrated in th is study. Both MoAbs were derived from patients with systemic lupus erythem atosus and anti-phospholipid antibody syndrome. The parallel analysis of th e specificity and affinity of four anti-phospholipid human MoAbs suggests t hat the binding of LJ1 MoAb to apoptotic cells is a specific property of th is MoAb. RSP-57 MoAb recognizes apoptotic cells through beta(2)-GPI which b ecomes available for binding after the interaction with negatively charged phospholipids. This observation provides evidence that the binding of human anti-phospholipid antibodies to apoptotic cells occurs in both a beta(2)-G PI-dependent and independent way and involves a restricted group of epitope s. The finding that LJ1 and RSP-57 MoAbs bind apoptotic cells underlines th e property of these MoAbs to act as cell membrane markers of apoptosis. Maj or pathological implications derive from the observation that LJ1 and RSP-5 7 MoAbs recognize epitopes expressed on 'early' apoptotic cells. The interf erence with the in vivo clearance and processing of apoptotic cells is a po tential pathogenic mechanism of these antibodies.