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A non-complement-fixing antibody to beta2 glycoprotein I as a novel therapy for antiphospholipid syndrome.

Authors: Agostinis, C  Durigutto, P  Sblattero, D  Borghi, MO  Grossi, C  Guida, F  Bulla, R  Macor, P  Pregnolato, F  Meroni, PL  Tedesco, F 
Citation: Agostinis C, etal., Blood. 2014 May 29;123(22):3478-87. doi: 10.1182/blood-2013-11-537704. Epub 2014 Mar 18.
Pubmed: (View Article at PubMed) PMID:24642748
DOI: Full-text: DOI:10.1182/blood-2013-11-537704

A single-chain fragment variable (scFv) recognizing beta2-glycoprotein 1 (beta2GPI) 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 beta2GPI 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-beta2GPI 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-beta2GPI antibodies from APS patients and displaced beta2GPI-bound patient antibodies. The CH2-deleted antibody represents an innovative approach potentially useful to treat APS patients refractory to standard therapy.

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CRRD Object Information
CRRD ID: 10054118
Created: 2015-07-28
Species: All species
Last Modified: 2015-07-28
Status: ACTIVE



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