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Pharmacodynamics of interferon beta in multiple sclerosis patients with or without serum neutralizing antibodies

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Abstract

To analyze the in vivo biological effect of anti-interferon beta (IFN-beta) neutralizing antibodies (NABs), blood concentrations of neopterin, beta2microglobulin (Beta2-MG), mRNA-dependent myxovirusresistant protein A (MxA) and dsRNA-dependent protein kinase (PKR) were measured before (predose) and 24 hours after (postdose) IFN-beta administration in 49 patients with multiple sclerosis (MS) with (n = 25) and without (n = 24) NABs.

The results indicated that predose levels of MxA-mRNA and PKR-mRNA were highly variable [coefficient of variation (CV) > 100%] among patients. A lower inter-individual variability was observed for pre-dose levels of Beta2-MG and neopterin (CVs of 29% and 44%, respectively).

Significantly lower pre- and post-dose blood levels of IFN induced markers, except for postdose PKR-mRNA (p = 0.09), were seen in NAB+ compared with NAB–patients and between patients with high (> 200 t1/10) and low (£ 200 t1/10) NAB titers. A significant inverse correlation between NAB titer and pre-dose levels of the above IFN-induced markers was found. In summary, our findings confirm that NABs affect absolute concentrations of IFN-beta induced markers and suggest that such an effect occurs in a titer-dependent manner.

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Authors and Affiliations

  1. Dept. of Experimental Medicine -Virology Section, “La Sapienza-University, Rome, Italy

    Carolina Scagnolari, Gabriella De Vito, Alessia Alberelli & Guido Antonelli

  2. Dept. of Neurology and Research, University Hospital, Basel, Switzerland

    Petra Duda MD & Ludwig Kappos MD

  3. Neuroimmunology Branch, NINDS, NIH, Bethesda, USA

    Francesca Bagnato & Valentina Durastanti

  4. Dept. of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy

    Vito Lavolpe & Maria Trojano

  5. National Institute for Infectious Diseases “L. Spallanzani, Rome, Italy

    Enrico Girardi

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  1. Carolina Scagnolari
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Correspondence to Ludwig Kappos MD.

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Scagnolari, C., Duda, P., Bagnato, F. et al. Pharmacodynamics of interferon beta in multiple sclerosis patients with or without serum neutralizing antibodies. J Neurol 254, 597–604 (2007). https://doi.org/10.1007/s00415-006-0332-7

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  • DOI: https://doi.org/10.1007/s00415-006-0332-7

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