Anti-coagulation effect of Fc fragment against anti-β2-GP1 antibodies in mouse models with APS

• Published in: International immunopharmacology 2011, Vol.11 (1), p.136-140
• Main Authors: Xie, Weidong, Zhang, Yaou, Bu, Cunya, Sun, Shijing, Hu, Shaoliang, Cai, Guoping
• Format: Article
• Language: English
• Subjects: Animals; Anti-β2-GP1 antibody; Antibodies, Antiphospholipid - blood; Anticoagulants - administration & dosage; Anticoagulants - immunology; Anticoagulants - therapeutic use; Antiphospholipid syndrome; Antiphospholipid Syndrome - blood; Antiphospholipid Syndrome - drug therapy; Antiphospholipid Syndrome - immunology; beta 2-Glycoprotein I - immunology; Biological and medical sciences; Blood coagulation; Disease Models, Animal; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Fc fragments; Humans; Immunization, Passive; Immunoglobulin Fc Fragments - administration & dosage; Immunoglobulin Fc Fragments - immunology; Immunoglobulin Fc Fragments - therapeutic use; Immunoglobulins, Intravenous - administration & dosage; Immunoglobulins, Intravenous - immunology; Immunoglobulins, Intravenous - therapeutic use; Intravenous immunoglobulin; Male; Medical sciences; Mice; Mice, Inbred BALB C; Pharmacology. Drug treatments; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; Recombinant Proteins - therapeutic use
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2010.10.018

Anti-beta (2)-glycoprotein I (anti-β2-GP1) is one of the important pathogenesis factors responsible for thrombosis formation in patients with antiphospholipid syndrome (APS). Administration of intravenous immunoglobulin (IVIg) is a common method used to inhibit the abnormal antibody levels and decrease the mortality of APS in emergency situations. We hypothesize that the Fc fragment of IgG is the molecular structure responsible for these effects. The present study investigates the beneficial effects of both recombinant and natural human Fc fragments of heterogeneous IgG against human anti-β2-GP1 antibodies in mouse models with APS. Results showed that both recombinant and natural human Fc fragments moderately but significantly decreased the levels of serum anti-β2-GP1 antibodies and had anti-coagulation effects in human β2-GP1-immunized mice. Furthermore, both recombinant and natural human Fc fragments inhibited thrombosis formation and decreased mortality in mouse models infused intravenously with human anti-β2GP1 antibodies from patients with APS. Findings suggest that the Fc fragment might be one of the active structural units of heterogeneous IgG. Thus, recombinant human Fc fragment administration may be a useful treatment for individuals with APS. ► Both recombinant and natural Fc fragments exert an anti-coagulation effect against anti-β2-GP1 antibodies in APS animals. ► The Fc, instead of Fab, fragment might be an active structural unit of IgG. ► Recombinant human Fc fragment has potential for development as treatment for APS individuals in the future.