%0 Journal Article %J Blood %D 2014 %T A non-complement-fixing antibody to β2 glycoprotein I as a novel therapy for antiphospholipid syndrome. %A Agostinis, Chiara %A Durigutto, Paolo %A Sblattero, Daniele %A Borghi, Maria O %A Grossi, Claudia %A Guida, Filomena %A Bulla, Roberta %A Macor, Paolo %A Pregnolato, Francesca %A Meroni, Pier Luigi %A Tedesco, Francesco %K Abortion, Spontaneous %K Animals %K Antibodies, Monoclonal %K Antiphospholipid Syndrome %K Autoantigens %K beta 2-Glycoprotein I %K Complement Activation %K Complement System Proteins %K Human Umbilical Vein Endothelial Cells %K Humans %K Immunoglobulin G %K Male %K Mice %K Protein Binding %K Rats %K Recombinant Proteins %K Single-Chain Antibodies %K Thrombosis %K Trophoblasts %X

A single-chain fragment variable (scFv) recognizing β2-glycoprotein 1 (β2GPI) from humans and other species was isolated from a human phage display library and engineered to contain an IgG1 hinge-CH2-CH3 domain. The scFv-Fc directed against β2GPI domain I-induced thrombosis and fetal loss, thus mimicking the effect of antibodies from patients with antiphospholipid syndrome (APS). Complement is involved in the biological effect of anti-β2GPI scFv-Fc, as demonstrated by its ability to promote in vitro and in vivo complement deposition and the failure to induce vascular thrombosis in C6-deficient rats and fetal loss in C5-depleted mice. A critical role for complement was also supported by the inability of the CH2-deleted scFv-Fc to cause vessel occlusion and pregnancy failure. This antibody prevented the pathological effects of anti-β2GPI antibodies from APS patients and displaced β2GPI-bound patient antibodies. The CH2-deleted antibody represents an innovative approach potentially useful to treat APS patients refractory to standard therapy.

%B Blood %V 123 %P 3478-87 %8 2014 May 29 %G eng %N 22 %1 http://www.ncbi.nlm.nih.gov/pubmed/24642748?dopt=Abstract %R 10.1182/blood-2013-11-537704