TY - JOUR T1 - A non-complement-fixing antibody to β2 glycoprotein I as a novel therapy for antiphospholipid syndrome. JF - Blood Y1 - 2014 A1 - Agostinis, Chiara A1 - Durigutto, Paolo A1 - Sblattero, Daniele A1 - Borghi, Maria O A1 - Grossi, Claudia A1 - Guida, Filomena A1 - Bulla, Roberta A1 - Macor, Paolo A1 - Pregnolato, Francesca A1 - Meroni, Pier Luigi A1 - Tedesco, Francesco KW - Abortion, Spontaneous KW - Animals KW - Antibodies, Monoclonal KW - Antiphospholipid Syndrome KW - Autoantigens KW - beta 2-Glycoprotein I KW - Complement Activation KW - Complement System Proteins KW - Human Umbilical Vein Endothelial Cells KW - Humans KW - Immunoglobulin G KW - Male KW - Mice KW - Protein Binding KW - Rats KW - Recombinant Proteins KW - Single-Chain Antibodies KW - Thrombosis KW - Trophoblasts AB -

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.

VL - 123 IS - 22 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24642748?dopt=Abstract ER -