title: Autoantibodies to factor VIII with catalytic activity.
abstract: Hemophilia A is an X-linked, recessive, bleeding disorder caused by defective or deficient factor VIII (FVIII) molecules. Infusion of purified FVIII to patients with severe hemophilia A results in approximately 25% of the cases, in the emergence of anti-FVIII antibodies (inhibitors) that are known to neutralize the pro-coagulant activity of FVIII by steric hindrance. We recently reported on the proteolysis of FVIII by allo-antibodies in the plasma of high responder patients with severe hemophilia A, demonstrating a new mechanism by which FVIII inhibitors may prevent the pro-coagulant function of FVIII. Hemophilia is the first model where a direct link between the hydrolysis of the target molecule and the occurrence of the clinical manifestations may be established. It also represents the first example in humans, of the induction of catalytic antibodies following the exogenous administration of an antigen. The characterization of FVIII inhibitors as site-specific proteases may provide new approaches to the treatment of inhibitors.
authors.affiliation: INSERM, U430, Hôpital Broussais, 96, rue Didot, 75014 Paris, France.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.forename: Anastas
authors.initials: A
authors.lastname: Pashov
authors.forename: Dorothea
authors.initials: D
authors.lastname: Stahl
authors.forename: Johan
authors.initials: J
authors.lastname: Hoebeke
authors.forename: Michel D
authors.initials: MD
authors.lastname: Kazatchkine
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
mesh_terms: D017151:Antibodies, Catalytic / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D010450:Endopeptidases / Q000737:chemistry; D005169:Factor VIII / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology*; D006467:Hemophilia A / Q000097:blood / Q000276:immunology*; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry / Q000276:immunology
chemical_list: D017151:Antibodies, Catalytic; D001323:Autoantibodies; D007074:Immunoglobulin G; D005169:Factor VIII; D010450:Endopeptidases