Professional article

Prevalence and epitope specificity of non-neutralising antibodies in a large cohort of haemophilia A patients without inhibitors

Published inThrombosis and haemostasis, vol. 105, no. 6, p. 954-961
Publication date2011

Antibodies (inhibitors and non-neutralising antibodies [NNA]) directed against factor VIII (FVIII) remain the main iatrogenic complication in haemophilia A (HA) patients. Inhibitors reduce FVIII pro-coagulant properties, whereas NNA are directed against non-functional epitopes. NNA are poorly studied and their prevalence, epitope specificity and physiopathology inadequately defined. The aim of this study was first to evaluate NNA prevalence in a French retrospective multicentric series of 210 patients without inhibitors, then to determine their epitope specificity (against the heavy chain [HC] or the light chain [LC] of FVIII) and particularly to assess the prevalence of anti-B domain NNA using specifically designed x-MAP assays. NNA occurred in 18.1% of patients (38/210) and their prevalence was not influenced by the severity of the disease. Among the 38 patients with NNA, 73.7% had anti-FVIII Abs against the HC, 13.2% against the LC and 13.2% had anti-FVIII Abs against both chains. There is thus a clear immuno-dominance of the HC of FVIII in the epitope profile of NNA, whatever the severity of HA. The proportion of NNA that recognised the B domain was 18.4% (n=7/38). A multivariate analysis did not highlight differences in NNA occurrence between patients treated with recombinant FVIII or with plasma- derived FVIII (19.6% vs. 14.9%, p=0.53).

  • Adolescent
  • Adult
  • Aged
  • Antibodies/metabolism
  • Child
  • Child, Preschool
  • Disease Progression
  • Epitope Mapping
  • Epitopes/metabolism
  • Factor VIII/immunology/metabolism
  • Female
  • France
  • Hemophilia A/epidemiology/immunology/physiopathology
  • Humans
  • Immunodominant Epitopes/metabolism
  • Infant
  • Male
  • Middle Aged
  • Prevalence
  • Retrospective Studies
Citation (ISO format)
LEBRETON, A et al. Prevalence and epitope specificity of non-neutralising antibodies in a large cohort of haemophilia A patients without inhibitors. In: Thrombosis and haemostasis, 2011, vol. 105, n° 6, p. 954–961. doi: 10.1160/TH10-10-0668
Main files (1)
Article (Published version)
ISSN of the journal0340-6245

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