title: HLA class II genotype and factor VIII inhibitors in mild haemophilia A patients with an Arg593 to Cys mutation.
abstract: We evaluated inhibitor formation in a group of patients with mild haemophilia A caused by an Arg593 to Cys mutation. A remarkably high cumulative inhibitor incidence of 14% over 22 years was observed. Three of 49 patients developed transient, low-titre inhibitors, which remained below 2.0 BU mL(-1). Four patients with an Arg593 to Cys mutation developed high-titre inhibitors (>5.0 BU mL(-1)). Three of these patients have been described previously. In this study, we characterized inhibitory antibodies in a fourth patient with high-titre inhibitors. Epitope mapping studies revealed that antibodies were predominantly directed to the A2 domain of factor VIII. We addressed the role of human leucocyte antigen (HLA) class II alleles in inhibitor development in patients with an Arg593 to Cys mutation by HLA genotyping. In the group of inhibitor patients raised frequencies of HLA-DRB1*01 and HLA-DQB1*05 were observed that did not reached statistical significance. Our data suggest that inhibitor development in mild haemophilia A patients with an Arg593 to Cys mutation is not linked to HLA class II profile.
authors.affiliation: Department of Plasma Proteins, Sanquin Research at CLB, Amsterdam, The Netherlands.
authors.forename: W S
authors.initials: WS
authors.lastname: Bril
authors.forename: P E
authors.initials: PE
authors.lastname: MacLean
authors.forename: P H P
authors.initials: PH
authors.lastname: Kaijen
authors.forename: E N
authors.initials: EN
authors.lastname: van den Brink
authors.forename: N M
authors.initials: NM
authors.lastname: Lardy
authors.forename: K
authors.initials: K
authors.lastname: Fijnvandraat
authors.forename: M
authors.initials: M
authors.lastname: Peters
authors.forename: J
authors.initials: J
authors.lastname: Voorberg
mesh_terms: D000906:Antibodies / Q000032:analysis*; D018604:Epitope Mapping; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D005802:Genes, MHC Class II / Q000235:genetics*; D005838:Genotype; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*
chemical_list: D000906:Antibodies; D005169:Factor VIII