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Disease Markers
Volume 25 (2008), Issue 1, Pages 27-35
http://dx.doi.org/10.1155/2008/824640

Molecular Network Analysis of T-Cell Transcriptome Suggests Aberrant Regulation of Gene Expression by NF-κB As a Biomarker for Relapse of Multiple Sclerosis

Jun-ichi Satoh,1,2 Tamako Misawa,1 Hiroko Tabunoki,1 and Takashi Yamamura2

1Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Japan
2Department of Immunology, National Institute of Neuroscience, NCNP, Japan

Received 12 August 2008; Accepted 12 August 2008

Copyright © 2008 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.