title: The use of factor VIII/von Willebrand factor concentrate for immune tolerance induction in haemophilia A patients with high-titre inhibitors: association of clinical outcome with inhibitor epitope profile.
abstract: A retrospective chart review of 11 subjects with severe haemophilia A and high-titre inhibitors who received a von Willebrand factor-containing FVIII concentrate (VWF/FVIII) for immune tolerance induction (ITI) was accompanied by B cell inhibitor epitope mapping during 10/11 treatment courses. ITI was successful or partially successful in all seven subjects who received VWF/FVIII for initial ITI, and failed in all four subjects whose ITI with this product was initiated following treatment failure using recombinant factor VIII. Variables including age at inhibitor development and age at ITI initiation, interval between inhibitor detection and ITI initiation, titre at start of ITI, and peak historical titres prior to and during ITI were not statistically significant outcome predictors in this cohort. However, the B cell epitope specificity in all four successful and in one of two partially successful ITI subjects for whom information was available included the C2 and excluded the A2 domains. Conversely, FVIII B cell epitopes in one partially successful ITI and in all three failed ITI subjects for whom data were available mapped to both the C2 and the A2 domains. The FVIII B cell epitope profile was associated with ITI outcome in this VWF/FVIII-treated cohort. Its role in predicting ITI outcome and guiding choice of FVIII product for ITI requires further study.
authors: Department of Pediatrics, Weill Medical College of Cornell University, New York, USA.
authors: D A
authors: DA
authors: Greninger
authors: J M
authors: JM
authors: Saint-Remy
authors: M
authors: M
authors: Jacquemin
authors: A
authors: A
authors: Benhida
authors: D M
authors: DM
authors: DiMichele
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D018604:Epitope Mapping; D000939:Epitopes / Q000032:analysis; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use; D005838:Genotype; D006467:Hemophilia A / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D007231:Infant, Newborn; D012189:Retrospective Studies; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000627:therapeutic use*
chemical_list: D001323:Autoantibodies; D004338:Drug Combinations; D000939:Epitopes; D006490:Hemostatics; C509423:factor VIII, von Willebrand factor drug combination; D014841:von Willebrand Factor; D005169:Factor VIII