Human monoclonal anti-phospholipid antibodies selectively bind to membrane phospholipid and beta2-glycoprotein I (beta2-GPI) on apoptotic cells.
The ability of an anti-phospholipid (LJ1) and an anti-beta2-GPI (RSP-57) human MoAb to bind to apoptotic but not viable cells was demonstrated in this study. Both MoAbs were derived from patients with systemic lupus erythematosus and anti-phospholipid antibody syndrome. The parallel analysis of the specificity and affinity of four anti-phospholipid human MoAbs suggests that the binding of LJ1 MoAb to apoptotic cells is a specific property of this MoAb. RSP-57 MoAb recognizes apoptotic cells through beta2-GPI which becomes 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 beta2-GPI-dependent and independent way and involves a restricted group of epitopes. The finding that LJ1 and RSP-57 MoAbs bind apoptotic cells underlines the property of these MoAbs to act as cell membrane markers of apoptosis. Major pathological implications derive from the observation that LJ1 and RSP-57 MoAbs recognize epitopes expressed on 'early' apoptotic cells. The interference with the in vivo clearance and processing of apoptotic cells is a potential pathogenic mechanism of these antibodies.
Pittoni
V
V
Centre for Rheumatology/Bloomsbury Rheumatology Unit, Department of Medicine and Department of Haematology, University College London, London, UK.
Ravirajan
C T
CT
Donohoe
S
S
MacHin
S J
SJ
Lydyard
P M
PM
Isenberg
D A
DA
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D017209:Apoptosis / Q000276:immunology*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008563:Membrane Lipids / Q000276:immunology; D051379:Mice; D010743:Phospholipids / Q000276:immunology*; D020298:U937 Cells; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D008563:Membrane Lipids; D010743:Phospholipids; D053482:beta 2-Glycoprotein I