title: Factor IX inhibition and epitope localization of factor IX inhibitor antibodies in haemophilia B patients with anaphylactoid reactions.
abstract: We describe the results of immunological studies, reaction kinetics and epitope localization of six inhibitor antibodies to factor IX (FIX) developed in severe haemophilia B patients. Three of the six patients had suffered recent anaphylactoid reactions to FIX concentrates, two others had in the past and one had none. All six inhibitors rapidly inactivated FIX activity in vitro, and the prominent immunoglobulin (IgG) subclass of the antibody was IgG4 when analysed with ELISA. Interestingly, we found an additional IgG1 component in the antibody samples from the patients who had recently experienced anaphylactoid reactions to FIX. When analysed with Western blotting in these three patients, the IgG4 antibody bound with enhanced affinity to the heavy chain or the light chain of FIX, and in two of the three the IgG1 antibody also bound strongly to the FIX heavy chain. The results suggest that the heavy chain of FIX might play a more significant role than the light chain in the pathogenesis of anaphylactoid reactions in haemophilia B patients with FIX inhibitors.
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: S
authors.initials: S
authors.lastname: Kamisue
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: Y
authors.initials: Y
authors.lastname: Sawamoto
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: H
authors.initials: H
authors.lastname: Nakai
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: I
authors.initials: I
authors.lastname: Tanaka
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: M
authors.initials: M
authors.lastname: Shima
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: J
authors.initials: J
authors.lastname: Takamatsu
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: T
authors.initials: T
authors.lastname: Oguni
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: S
authors.initials: S
authors.lastname: Kinoshita
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: J C
authors.initials: JC
authors.lastname: Giddings
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara 634, Japan,Paediatric Clinic, Gose Saiseikai Hospital, Gose, Nara 639-22, Japan,Division of Blood Transfusion Medicine, Nagoya University, Faculty of Medicine, Nagoya 466, Japan,Paediatric Clinic, Hirakata City Hospital, Hirakata, Osaka 573, Japan,Paediatric Clinic, National Osaka Hospital, Osaka 540, Japan,Department of Haematology, University of Wales College of Medicine, Cardiff, Wales.
authors.forename: A
authors.initials: A
authors.lastname: Yoshioka
keywords: Western blot; anaphylactoid reaction; haemophilia B; immunoglobulin subclass; inhibitor