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

Aurélien Lebreton; Priscilla Lapalud; Hervé Chambost; Christine Biron-Andreani; Pierre-Emmanuel Morange; Christophe Combescure; Alain Marques-Verdier; Claire Berger; Jean-François Schved; Claude Granier; Géraldine Lavigne-Lissalde

doi:10.1160/TH10-10-0668

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 105(06): 954-961
DOI: 10.1160/TH10-10-0668

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

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

Aurélien Lebreton^*

¹UMR 3145 SysDiag CNRS/Bio-Rad, Parc Euromédecine, Montpellier, France

,

Priscilla Lapalud^*

¹UMR 3145 SysDiag CNRS/Bio-Rad, Parc Euromédecine, Montpellier, France

,

Hervé Chambost

²Haemophilia Treatment Centre, Children Hospital la Timone, Mediterranean University, Marseille, France

,

Christine Biron-Andreani

³Haemophilia Treatment Centre, University Hospital of Montpellier, France

,

Pierre-Emmanuel Morange

⁴Haematology Department, University Hospital La Timone, Marseille, France

,

Christophe Combescure

⁵Division of Clinical Epidemiology, University Hospital of Geneva and University of Geneva, Switzerland

,

Alain Marques-Verdier

⁶Haemophilia Treatment Centre, University Hospital of Clermont-Ferrand, France

,

Claire Berger

⁷Haemophilia Treatment Centre, University Hospital of Saint-Etienne, France

,

Jean-François Schved

³Haemophilia Treatment Centre, University Hospital of Montpellier, France

,

Claude Granier

¹UMR 3145 SysDiag CNRS/Bio-Rad, Parc Euromédecine, Montpellier, France

,

Géraldine Lavigne-Lissalde

¹UMR 3145 SysDiag CNRS/Bio-Rad, Parc Euromédecine, Montpellier, France

³Haemophilia Treatment Centre, University Hospital of Montpellier, France

› Author Affiliations

Abstract

Summary

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 procoagulant 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).

Keywords

Haemophilia A - factor VIII - x-MAP technology - non-neutralising antibodies - epitope mapping

Full Text

References

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