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In vivo bioactivity of interferon beta in multiple sclerosis patients with neutralizing antibodies is titer dependent
  1. Ajith Sominanda (ajith.sominanda{at}ki.se)
  1. Karolinska University Hospital Huddinge, Sweden
    1. Jan Hillert (jan.hillert{at}ki.se)
    1. Karolinska University Hospital Huddinge, Sweden
      1. Anna Fogdell-Hahn (anna.fogdell-hahn{at}ki.se)
      1. Karolinska University Hospital Huddinge, Sweden

        Abstract

        Background: Development of neutralizing antibodies (NAbs) against recombinant interferon-b (IFNb) is a significant clinical problem in the treatment of multiple sclerosis (MS). Several methods are available to assess NAbs, but there is lack of consensus on how the different NAb titer levels interfere with the efficacy of the drug, especially in the individual patient.

        Methods: NAb titers were measured with an in vitro MxA induction assay and in vivo IFNb response was assessed by measuring MxA mRNA expression using real-time PCR.

        Results: We identified titer levels of NAbs at which the IFNb biological activity was reduced or abrogated. Patients with NAb titers up to 150 TRU/ml (ten times reduction units per ml) still had retained IFNb bioactivity, whereas greatly reduced levels of IFNb bioactivity were found in patients with NAbs between 150 and 600 TRU/ml. Titers above 600 TRU/ml were associated with loss of IFNb bioactivity. Similar results were obtained when TRAIL mRNA was used as a marker of the in vivo response to IFNb.

        Conclusion: There is a stepwise loss of IFNb bioactivity with increasing NAb titers and it is possible to identify functionally critical NAb titer levels that are useful as a support in treatment decisions at the individual patient level.

        • In vivo bioactivity
        • Interferon beta
        • Multiple sclerosis
        • MxA induction assay
        • Neutralizing antibodies (NAbs)

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