Baseline MxA mRNA expression predicts interferon beta response in multiple sclerosis patients

PLoS One. 2014 Nov 14;9(11):e112758. doi: 10.1371/journal.pone.0112758. eCollection 2014.

Abstract

Background: Myxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection, mostly used to evaluate its bioactivity. There is little available data on clinical utility of baseline MxA mRNA status. The objective of the study is to investigate whether baseline MxA mRNA expression can predict relapse and disease progression in multiple sclerosis patients treated with interferon-beta.

Methods: Baseline blood samples were obtained before the first interferon-beta dose was administered to evaluate MxA mRNA expression using real-time polymerase chain reaction (PCR). Demographic and clinical variables were prospectively recorded to define treatment responder and non responder groups.

Results: 104 patients were included in the study. Baseline MxA mRNA expression was significantly lower in the group of patients who met the definition of responders (1.07 vs 1.95, Student t test, p<0.0001). A threshold of 1.096 was established using Receiver Operating Characteristic analysis to differentiate between responders and non-responders (sensitivity 73.9%, specificity 69.0%). Survival analysis using this threshold showed that time to next relapse (p<0.0001) and to EDSS progression (p = 0.01) were significantly higher in patients with lower MxA titers.

Conclusion: The results suggest that baseline MxA mRNA levels may be useful for predicting whether multiple sclerosis patients will respond or not to interferon-beta treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • Humans
  • Interferon-beta / administration & dosage
  • Interferon-beta / immunology
  • Interferon-beta / pharmacology*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Myxovirus Resistance Proteins / genetics
  • Myxovirus Resistance Proteins / metabolism*
  • RNA, Messenger / blood*
  • RNA, Messenger / genetics
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Surveys and Questionnaires
  • Survival Analysis

Substances

  • Biomarkers
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • RNA, Messenger
  • Interferon-beta

Grants and funding

This work was supported by the Convenio de Investigación, Dep. de Salut, Generalitat de Catalunya (grant number 352/05). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.