Journal of Neurology

, Volume 254, Issue 5, pp 597–604

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

  • Carolina Scagnolari
  • Petra Duda
  • Francesca Bagnato
  • Gabriella De Vito
  • Alessia Alberelli
  • Vito Lavolpe
  • Enrico Girardi
  • Valentina Durastanti
  • Maria Trojano
  • Ludwig Kappos
  • Guido Antonelli
ORIGINAL COMMUNICATION

DOI: 10.1007/s00415-006-0332-7

Cite this article as:
Scagnolari, C., Duda, P., Bagnato, F. et al. J Neurol (2007) 254: 597. doi:10.1007/s00415-006-0332-7

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.

Key words

interferon betaneutralizing antibodiesmultiple sclerosisMxAPKRBeta2-microglobulinneopterin

Copyright information

© Steinkopff-Verlag 2007

Authors and Affiliations

  • Carolina Scagnolari
    • 1
  • Petra Duda
    • 2
  • Francesca Bagnato
    • 3
  • Gabriella De Vito
    • 1
  • Alessia Alberelli
    • 1
  • Vito Lavolpe
    • 4
  • Enrico Girardi
    • 5
  • Valentina Durastanti
    • 3
  • Maria Trojano
    • 4
  • Ludwig Kappos
    • 2
  • Guido Antonelli
    • 1
  1. 1.Dept. of Experimental Medicine -Virology Section“La Sapienza-UniversityRomeItaly
  2. 2.Dept. of Neurology and ResearchUniversity HospitalBaselSwitzerland
  3. 3.Neuroimmunology Branch, NINDS, NIHBethesdaUSA
  4. 4.Dept. of Neurological and Psychiatric SciencesUniversity of BariBariItaly
  5. 5.National Institute for Infectious Diseases “L. SpallanzaniRomeItaly