title: A non-complement-fixing antibody to β2 glycoprotein I as a novel therapy for antiphospholipid syndrome.
abstract: 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.
authors.affiliation: Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo, Trieste, Italy;
authors.forename: Chiara
authors.initials: C
authors.lastname: Agostinis
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: Durigutto
authors.affiliation: Department Health Sciences and Research Institute Against Digestive Cancer, University of Eastern Piedmont, Novara, Italy;
authors.forename: Daniele
authors.initials: D
authors.lastname: Sblattero
authors.affiliation: Laboratory of Immuno-Rheumatology, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Maria O
authors.initials: MO
authors.lastname: Borghi
authors.affiliation: Laboratory of Immuno-Rheumatology, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; and.
authors.forename: Claudia
authors.initials: C
authors.lastname: Grossi
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy;
authors.forename: Filomena
authors.initials: F
authors.lastname: Guida
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy;
authors.forename: Roberta
authors.identifier: http://orcid.org/0000-0003-1737-5776
authors.initials: R
authors.lastname: Bulla
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: Macor
authors.affiliation: Laboratory of Immuno-Rheumatology, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; and.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pregnolato
authors.affiliation: Laboratory of Immuno-Rheumatology, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Meroni
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy;
authors.forename: Francesco
authors.identifier: http://orcid.org/0000-0003-2462-0493
authors.initials: F
authors.lastname: Tedesco
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D016736:Antiphospholipid Syndrome / Q000188:drug therapy* / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use; D057127:Single-Chain Antibodies / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use; D013927:Thrombosis / Q000276:immunology; D014327:Trophoblasts; D053482:beta 2-Glycoprotein I / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D001324:Autoantigens; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies; D053482:beta 2-Glycoprotein I; D003165:Complement System Proteins