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Biological considerations of plasma-derived and recombinant factor VIII immunogenicity

Jesse Lai, Christine Hough, Julie Tarrant and David Lillicrap

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  • RE: Is the combination of isolated FVIII and isolated VWF equivalent to the natural FVIII/VWF complex?
    • Maria Isabel Bravo, R&D Scientist Grifols
    • Other Contributors:
      • Ana María Ortiz, R&D Scientist
      • Montserrat Costa, R&D Scientist
      • Salvador Grancha, R&D Scientist
      • Juan I Jorquera, R&D Scientist

    In their recent report [1], Lai J et al presented and discussed a range of biological mechanisms, providing a valuable summary of the increasingly convincing evidence of immunogenic differences between factor VIII concentrates [2], i.e. plasma-derived, von Willebrand Factor-containing (pdFVIII/VWF) and recombinant (rFVIII). As Lai et al remark, the evidence that supports the potential immune-protective role played by VWF for FVIII point predominantly to the inhibition of endocytosis of pdFVIII/VWF by dendritic cells. Interestingly, in their discussion the authors highlight the potential structural differences between the in vitro mixtures of FVIII and VWF and the complex that these two molecules may form in vivo. We believe that this is a crucial aspect that deserves further examination. Besides FVIII immunogenicity, important data on FVIII antigenicity once the inhibitor is already present in plasma, are also available. Recently, our group analyzed the reactivity against inhibitors in concentrates with native pdFVIII/VWF compared to several purified FVIII concentrates, including pdFVIII and rFVIII [3,4].

    Results showed that native pdFVIII/VWF complex had lower sensitivity to inhibitors than the combination in vitro of isolated FVIII and VWF proteins [4] (Table 1). However, the most intriguing point was that the results were independent on whether FVIII was adde...

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    Conflict of Interest:
    The authors are employees of Grifols, a manufacturer of plasmatic FVIII/VWF concentrate. Medical writing and editorial support was provided by Jordi Bozzo PhD, CMPP (Grifols).