RGD Reference Report - A non-complement-fixing antibody to beta2 glycoprotein I as a novel therapy for antiphospholipid syndrome. - Rat Genome Database

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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.
RGD ID: 10054118
Pubmed: PMID:24642748   (View Abstract at PubMed)
DOI: DOI:10.1182/blood-2013-11-537704   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Apoh  (apolipoprotein H)

Genes (Mus musculus)
Apoh  (apolipoprotein H)

Genes (Homo sapiens)
APOH  (apolipoprotein H)


Additional Information