Characterization of factor VIII inhibitors

International Journal of Hematology
M Shima

Abstract

Factor VIII (FVIII) inhibitors develop as either alloantibodies against exogenous FVIII in patients with congenital hemophilia A after FVIII-replacement therapy or as autoantibodies against endogenous FVIII in previously healthy, nonhemophilic individuals. The predominant immunoglobulin G (IgG) subclass of FVIII inhibitors is IgG(4). The main epitopic regions are known to be located, however, in the A2, A3, and C2 domains. The A2 and A3 epitopes have been identified between amino acid residues 484 and 509 and residues 558 and 565, respectively. Both of these regions are close to the binding sites for activated FIX (FIXa). Two regions have been identified in the C2 domain, one in the amino-terminal portion of the domain (residues 2181-2243) and the other in the carboxy-terminal portion of the domain (residues 2248-2312 and residues 2315-2330). In addition, a crystallographic analysis of a complex of the C2 domain and a human monoclonal IgG(4)(K) Fab revealed that this type of antibody is in direct contact with hydrophobic and basic residues of the membrane-binding surface. Inactivated FVIII is rapidly cleared from the circulation in the presence of inhibitors. The inhibitors also bind to essential FVIII ligand proteins, includin...Continue Reading

References

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Citations

Aug 25, 2012·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Eunjung KangHyun Woo Lee
Aug 19, 2008·The Journal of Dermatology·Osao ArakakiHiroshi Uezato
Apr 9, 2010·Journal of Thrombosis and Haemostasis : JTH·J D DimitrovS Lacroix-Desmazes
Jun 8, 2018·Internal Medicine·Jun YamanouchiMasaki Yasukawa

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