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A LIMITED NUMBER OF ANTI-IDIOTYPIC ANTIBODIES NEUTRALIZE FVIII INHIBITORS AND RESTORE FULL FVIII ACTIVITY IN THE PLASMA OF HAEMOPHILIA PATIENTS
Abstract number: O-M-017
Gilles1 J.G., Grailly1 S.C., Jacquemin1 M.G., Saint-Remy1 J.M.
1Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
How-to-cite Gilles JG, Grailly SC, Jacquemin MG, Saint-Remy JM. A LIMITED NUMBER OF ANTI-IDIOTYPIC ANTIBODIES NEUTRALIZE FVIII INHIBITORS AND RESTORE FULL FVIII ACTIVITY IN THE PLASMA OF HAEMOPHILIA PATIENTS. J Thromb Haemost 2007; 5 Supplement 2: O-M-017
Abstract
Introduction: Replacement therapy using FVIII elicits FVIII-specific antibodies (abs) in about 25% of the patients. The majority of such abs are directed towards specific FVIII regions on which major epitopes have been identified. Most of them are located in the carboxy-terminal end of the C2 domain of the FVIII and in the amino-terminal end of the A2 domain, whereas, abs directed towards the C1 domain have been described in cases of mild/moderate haemophilia A.
Methods: We derived human monoclonal abs (mabs) that react with high affinity to the FVIII C1, C2 and A2 domains and are representative of most of the specific inhibitors observed in haemophilia A patients. We generated mouse anti-idiotypic mabs (anti-Ids) against the paratope of each of them.
Results: We first demonstrated that FVIII inhibition obtained by a mixture of two anti-FVIII mabs (anti-C2 and anti-A2) was neutralized up to 100% when a mixture of the corresponding anti-Ids was added to the assay.
We next evaluated whether a combination of anti-Ids (anti-anti-A2,-C1,-C2) had the ability to neutralize the inhibitory properties of polyclonal abs in plasma. To this end, eighteen plasmas from haemophilia patients with inhibitor (14 with alloabs and 4 with autoabs) were tested. In 16 out of the 18 cases, the inhibiting FVIII activity from the plasma was neutralized up to 100% by the anti-Ids mixture and full FVIII activity was restored.
Conclusions: These data allow to conclude that potent polyclonal high-affinity FVIII inhibitors can be neutralized with an anti-Ids mixture and that only a limited number of anti-Ids is required for inhibitor neutralization of 90% of the patients.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
Session Details
| Date: |
01/08/2007
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| Time: |
00:00-00:00
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| Session name: |
XXIst ISTH Congress |
| Subject: |
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| Location: |
Oxford, UK |
| Presentation type: |
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