title: Baseline gene expression signatures in monocytes from multiple sclerosis patients treated with interferon-beta.
abstract: BACKGROUND
  A relatively large proportion of relapsing-remitting multiple sclerosis (RRMS) patients do not respond to interferon-beta (IFNb) treatment. In previous studies with peripheral blood mononuclear cells (PBMC), we identified a subgroup of IFNb non-responders that was characterized by a baseline over-expression of type I IFN inducible genes. Additional mechanistic experiments carried out in IFNb non-responders suggested a selective alteration of the type I IFN signaling pathway in the population of blood monocytes. Here, we aimed (i) to investigate whether the type I IFN signaling pathway is up-regulated in isolated monocytes from IFNb non-responders at baseline; and (ii) to search for additional biological pathways in this cell population that may be implicated in the response to IFNb treatment.
  
  
  METHODS
  Twenty RRMS patients classified according to their clinical response to IFNb treatment and 10 healthy controls were included in the study. Monocytes were purified from PBMC obtained before treatment by cell sorting and the gene expression profiling was determined with oligonucleotide microarrays.
  
  
  CONCLUSIONS
  Purified monocytes from IFNb non-responders were characterized by an over-expression of type I IFN responsive genes, which confirms the type I IFN signature in monocytes suggested from previous studies. Other relevant signaling pathways that were up-regulated in IFNb non-responders were related with the mitochondrial function and processes such as protein synthesis and antigen presentation, and together with the type I IFN signaling pathway, may also be playing roles in the response to IFNb.
authors: Servei de Neurología/Neuroimmunología. Centre d'Esclerosi Múltiple de Catalunya, Cemcat. Hospital Universitari Vall dHebron (HUVH), Barcelona, Spain.
authors: Marta F
authors: MF
authors: Bustamante
authors: Ramil N
authors: RN
authors: Nurtdinov
authors: Jordi
authors: J
authors: Río
authors: Xavier
authors: X
authors: Montalban
authors: Manuel
authors: M
authors: Comabella
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000502:physiology; D009000:Monocytes / Q000378:metabolism*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000503:physiopathology*; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D007370:Interferon Type I; D016899:Interferon-beta
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