Myxovirus Resistance Protein A mRNA Expression Kinetics in Multiple Sclerosis Patients Treated with IFNβ

PLoS One. 2017 Jan 12;12(1):e0169957. doi: 10.1371/journal.pone.0169957. eCollection 2017.

Abstract

Introduction: Interferon-β (IFNß) is the first-line treatment for relapsing-remitting multiple sclerosis. Myxovirus resistance protein A (MxA) is a marker of IFNß bioactivity, which may be reduced by neutralizing antibodies (NAbs) against IFNß. The aim of the study was to analyze the kinetics of MxA mRNA expression during long-term IFNβ treatment and assess its predictive value.

Methods: A prospective, observational, open-label, non-randomized study was designed in multiple sclerosis patients starting IFNß treatment. MxA mRNA was assessed prior to initiation of IFNß therapy and every three months subsequently. NAbs were assessed every six months. Assessment of relapses was scheduled every three months during 24 months of follow up. The disease activity was correlated to the pretreatment baseline MxA mRNA value. In NAb negative patients, clinical status was correlated to MxA mRNA values.

Results: 119 patients were consecutively enrolled and 107 were included in the final analysis. There was no correlation of MxA mRNA expression levels between baseline and month three. Using survival analysis, none of the selected baseline MxA mRNA cut off points allowed prediction of time to first relapse on the treatment. In NAb negative patients, mean MxA mRNA levels did not significantly differ in patients irrespective of relapse status.

Conclusion: Baseline MxA mRNA does not predict the response to IFNß treatment or the clinical status of the disease and the level of MxA mRNA does not correlate with disease activity in NAb negative patients.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing / blood
  • Area Under Curve
  • Female
  • Humans
  • Injections, Intramuscular
  • Injections, Subcutaneous
  • Interferon beta-1a / administration & dosage
  • Interferon beta-1a / therapeutic use*
  • Kinetics
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology
  • Myxovirus Resistance Proteins / genetics*
  • Myxovirus Resistance Proteins / metabolism
  • Prospective Studies
  • RNA, Messenger / metabolism
  • ROC Curve
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Myxovirus Resistance Proteins
  • RNA, Messenger
  • Interferon beta-1a

Grants and funding

The work has been supported by grant project IGA MZ CR NT/12385-5, http://www.mzcr.cz/Odbornik/dokumenty/vyhlaseni-vysledku-ves-2011-2015-na-zaklade-rozhodnuti-ministra-zdravotnictvi_4868_1749_3.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.