Molecular network analysis of T-cell transcriptome suggests
aberrant regulation of gene expression by NF-κB as a biomarker for
relapse of multiple sclerosis
Affiliations: Department of Bioinformatics and Molecular
Neuropathology, Meiji Pharmaceutical University, Japan | Department of Immunology, National Institute of
Neuroscience, NCNP, Japan
Note: [] Corresponding author: Prof. Dr. Jun-ichi Satoh, Department of
Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University,
2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. Tel./Fax: +81 42 495 8678;
E-mail: satoj@my-pharm.ac.jp
Abstract: 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-κB) in T cells during MS relapse. These
results support the logical hypothesis that NF-κB 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-κB on
T-cell transcriptome might serve as a molecular biomarker for monitoring the
clinical disease activity of MS.
Keywords: KeyMolnet, multiple sclerosis, nuclear factor-kappa B, relapse, T cells
