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

Lebreton, A
Lapalud, P
Chambost, H
Biron-Andréani, C
Morange, P-E
Marquès-Verdier, A
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Published in Thrombosis and haemostasis. 2011, vol. 105, no. 6, p. 954-61
Abstract 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).
Keywords AdolescentAdultAgedAntibodies/metabolismChildChild, PreschoolDisease ProgressionEpitope MappingEpitopes/metabolismFactor VIII/immunology/metabolismFemaleFranceHemophilia A/epidemiology/immunology/physiopathologyHumansImmunodominant Epitopes/metabolismInfantMaleMiddle AgedPrevalenceRetrospective Studies
PMID: 21475776
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Research group Epidémiologie clinique (115)
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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. 954-61. doi: 10.1160/TH10-10-0668 https://archive-ouverte.unige.ch/unige:25665

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Deposited on : 2013-01-17

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