RESEARCH - Anti-endothelial antibodies interfere in apoptotic cell clearance and promote thrombosis in antiphospholipid syndrome

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J Immunol. 2009 Feb 1;182(3):1756-62.

Anti-endothelial antibodies interfere in apoptotic cell clearance and

promote thrombosis in patients with antiphospholipid syndrome.

Graham A, Ford I, on R, Barker RN, Greaves M, Erwig LP.

School of Medicine, Division of Applied Medicine, University of

Aberdeen, United Kingdom.

Antiphospholipid syndrome is an important cause of recurrent

thrombotic events. The pathogenesis of the thrombosis remains unclear,

but it has been suggested that anti-phospholipid Abs, which are

laboratory markers for the disease and include species capable of

binding to vascular endothelial cells, play an important role. We

hypothesized that these anti-endothelial Abs promote thrombosis

through interference with clearance of dying cells. We show that

healthy endothelial cell monolayers effectively remove apoptotic

endothelial cells, but this clearance is markedly inhibited by serum

or IgG from patients with antiphospholipid syndrome and

anti-endothelial Abs. In addition, patient sera or IgG opsonize

apoptotic endothelial cells and cause enhanced Fc-mediated uptake by

professional phagocytes. Importantly, the delayed clearance of

apoptotic cells by healthy endothelial cells and the enhanced

Fc-mediated macrophage uptake each result in procoagulant

consequences, as judged by increased thrombin generation. The effects

on apoptotic cell clearance were reproduced by a mAb derived from a

patient with antiphospholipid syndrome, which binds to endothelial

cells and is thrombogenic in experimental models. Taken together, our

data support a novel, dual mechanism by which anti-endothelial Abs are

prothrombotic in antiphospholipid syndrome by inhibiting removal of

procoagulant apoptotic cells and by diverting their clearance to

provoke inflammatory and prothrombotic changes in professional

phagocytes.

PMID: 19155525

http://www.ncbi.nlm.nih.gov/pubmed/19155525

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