Molecular network analysis of T-cell transcriptome suggests aberrant regulation of gene expression by NF-kappaB as a biomarker for relapse of multiple sclerosis

Dis Markers. 2008;25(1):27-35. doi: 10.1155/2008/824640.


Molecular mechanisms responsible for acute relapse of multiple sclerosis (MS) remain currently unknown. The aim of this study is to identify the relapse-specific biomarker genes in T lymphocytes of relapsing-remitting MS (RRMS). Total RNA of CD3+ T cells isolated from six RRMS patients taken at the peak of acute relapse and at the point of complete remission was processed for DNA microarray analysis. We identified a set of 43 differentially expressed genes (DEG) between acute relapse and complete remission. By using 43 DEG as a discriminator, hierarchical clustering separated the cluster of relapse from that of remission. The molecular network of 43 DEG investigated by KeyMolnet, a bioinformatics tool for analyzing molecular interaction on the curated knowledge database, showed the most significant relationship with aberrant regulation of gene expression by the nuclear factor-kappa B (NF-kappaB) in T cells during MS relapse. These results support the logical hypothesis that NF-kappaB plays a central role in triggering molecular events in T cells responsible for induction of acute relapse of MS, and suggest that aberrant gene regulation by NF-kappaB on T-cell transcriptome might serve as a molecular biomarker for monitoring the clinical disease activity of MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers*
  • CD3 Complex / biosynthesis
  • Cluster Analysis
  • Female
  • Gene Expression Profiling
  • Humans
  • Models, Biological
  • Models, Statistical
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / therapy
  • NF-kappa B / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Recurrence
  • Remission Induction
  • T-Lymphocytes / metabolism*
  • Transcription, Genetic*


  • Biomarkers
  • CD3 Complex
  • NF-kappa B