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A non-complement-fixing antibody to β2 glycoprotein I as a novel therapy for antiphospholipid syndrome.
- Source :
-
Blood [Blood] 2014 May 29; Vol. 123 (22), pp. 3478-87. Date of Electronic Publication: 2014 Mar 18. - Publication Year :
- 2014
-
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.<br /> (© 2014 by The American Society of Hematology.)
- Subjects :
- Abortion, Spontaneous immunology
Animals
Antibodies, Monoclonal genetics
Complement Activation drug effects
Complement Activation immunology
Human Umbilical Vein Endothelial Cells
Humans
Immunoglobulin G immunology
Male
Mice
Protein Binding immunology
Rats
Recombinant Proteins immunology
Recombinant Proteins isolation & purification
Recombinant Proteins therapeutic use
Single-Chain Antibodies immunology
Single-Chain Antibodies isolation & purification
Single-Chain Antibodies therapeutic use
Thrombosis immunology
Trophoblasts
beta 2-Glycoprotein I metabolism
Antibodies, Monoclonal immunology
Antibodies, Monoclonal therapeutic use
Antiphospholipid Syndrome drug therapy
Antiphospholipid Syndrome immunology
Autoantigens immunology
Complement System Proteins immunology
beta 2-Glycoprotein I immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 123
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 24642748
- Full Text :
- https://doi.org/10.1182/blood-2013-11-537704