A non-complement-fixing antibody to β2 glycoprotein i as a novel therapy for antiphospholipid syndrome

Chiara Agostinis, Paolo Durigutto, Daniele Sblattero, Maria O. Borghi, Claudia Grossi, Filomena Guida, Roberta Bulla, Paolo Macor, Francesca Pregnolato, Pier Luigi Meroni, Francesco Tedesco

Research output: Contribution to journalArticlepeer-review

Abstract

Asingle-chain fragment variable(scFv) recognizing β2-glycoprotein1 (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-depletedmice. 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.

Original languageEnglish
Pages (from-to)3478-3487
Number of pages10
JournalBlood
Volume123
Issue number22
DOIs
Publication statusPublished - May 29 2014

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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