Bioavailability of interferon beta 1b in MS patients with and without neutralizing antibodies

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Abstract
Background: Neutralizing antibodies (NAB) to interferon beta (IFNβ) occur in about one-third of MS patients treated with IFNβ-1b and there is an association with a loss of clinical and MRI efficacy. However, there are no data regarding the bioavailability of IFNβ-1b in patients with and without NAB. Methods: The authors measured MxA in whole blood by ELISA, and serum-binding antibodies (SBA) by Western blot and ELISA in 134 samples of MS patients on IFNβ-1b and 54 control subjects, and correlated the MxA levels and SBA titers with the NAB titer. Results: In the IFNβ group 84 samples were NAB negative, 21 were NAB positive (i.e., titer of ≥20), and 29 had detectable NAB (i.e., titer between 10 and 20). The median MxA concentration in NAB-negative patients was 4.09 ng/105 peripheral blood leukocytes (PBL), 2.37 ng/105 PBL in samples with detectable NAB, 0.36 ng/105 PBL in NAB-positive samples, and 0.27 ng/105 PBL in control subjects. There was no significant difference between NAB-positive samples and control subjects, otherwise the groups differed significantly from each other. SBA occurred in 49% of NAB-negative samples, in 79% of samples with detectable NAB, and in all NAB-positive samples. With regard to the SBA titer, all groups differed significantly from each other. In none of the control samples were SBA detected. Conclusion: The conversion of SBA into NAB depends to some degree on the SBA titer, but other mechanisms may be involved. Once NAB have developed, the bioavailability of IFNβ as measured by MxA is completely inhibited.