Free Content Human monoclonal anti-phospholipid antibodies selectively bind to membrane phospholipid and β2-glycoprotein I (β2-GPI) on apoptotic cells

Authors: Pittoni, V.1; Ravirajan, C. T.1; Donohoe, S.2; Machin, S. J.2; Lydyard, P. M.1; Isenberg, D. A.1

Source: Clinical & Experimental Immunology, Volume 119, Number 3, March 2000 , pp. 533-543(11)

Publisher: Blackwell Publishing

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Abstract:

The ability of an anti-phospholipid (LJ1) and an anti-β2-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 β2-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 β2-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.

Keywords: apoptosis; autoantibodies; phospholipid; anti-phospholipid; antibody; β2-glycoprotein I

Document Type: Research article

DOI: 10.1046/j.1365-2249.2000.01161.x

Affiliations: 1: Centre for Rheumatology/Bloomsbury Rheumatology Unit, Department of Medicine and 2: Department of Haematology, University College London, London, UK

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