Molecular network analysis of T-cell transcriptome suggests aberrant regulation of gene expression by NF-kappaB as a biomarker for relapse of multiple sclerosis.
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.
Satoh
Jun-ichi
J
Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Japan. satoj@my-pharm.ac.jp
Misawa
Tamako
T
Tabunoki
Hiroko
H
Yamamura
Takashi
T
D000328:Adult; D015415:Biomarkers; D017252:CD3 Complex / Q000096:biosynthesis; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D016328:NF-kappa B / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012008:Recurrence; D012074:Remission Induction; D013601:T-Lymphocytes / Q000378:metabolism*; D014158:Transcription, Genetic
D015415:Biomarkers; D017252:CD3 Complex; D016328:NF-kappa B