Microarray detection of E2F pathway activation and other targets in multiple sclerosis peripheral blood mononuclear cells

J Neuroimmunol. 2004 May;150(1-2):163-77. doi: 10.1016/j.jneuroim.2004.01.017.

Abstract

We performed microarray analysis of peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients and detected a profile of immune cell activation, autoantigen upregulation, and enhanced E2F pathway transcription. Accordingly, E2f1-deficient mice manifested only mild disability upon induction of experimental autoimmune encephalomyelitis (EAE). Furthermore, PBMCs from Avonex-treated patients had lower expression of E2F targets. The profile was enriched in genes known to harbor MS-associated polymorphisms, or localized to MS susceptibility chromosomal regions. Our study shows that PBMC microarrays reflect MS pathobiology that can be validated in the EAE model.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Cell Cycle Proteins*
  • Chromosome Mapping
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Female
  • Gene Expression Profiling* / methods
  • Gene Expression Profiling* / statistics & numerical data
  • Humans
  • Interferon beta-1a
  • Interferon-beta / therapeutic use
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Multigene Family / drug effects
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / genetics*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / metabolism*
  • Oligonucleotide Array Sequence Analysis* / methods
  • Oligonucleotide Array Sequence Analysis* / statistics & numerical data
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Signal Transduction / immunology
  • Transcription Factors / deficiency
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2f1 protein, mouse
  • Transcription Factors
  • Interferon-beta
  • Interferon beta-1a