title: Differential microRNA expression in blood in multiple sclerosis.
abstract: BACKGROUND
  microRNAs (miRNAs) regulate the expression of the genome at the post-transcriptional level. They play a role in autoimmunity and inflammation, and show potential for use as therapeutic targets in many diseases. With the recent detection of miRNAs in body fluids, the possibility for using miRNAs as diagnostic biomarkers has emerged.
  
  
  OBJECTIVE
  We assessed whether miRNAs contribute to the altered immune activation state in relapsing-remitting multiple sclerosis (RRMS) patients and investigated the possible use of miRNAs as diagnostic biomarkers in multiple sclerosis (MS).
  
  
  METHODS
  We performed global miRNA expression profiling analysis in peripheral blood mononuclear cells (PBMCs) and selected miRNAs were measured in plasma. We detected expression of miRNAs by real-time qPCR and compared results with cytokines related to inflammation and disease activity. Selected miRNAs were analyzed in PBMC subpopulations, after isolating them by magnetic bead separation.
  
  
  RESULTS
  We found that among validated miRNAs, let-7d correlated with the pro-inflammatory cytokine interleukin-1B. The miR-145 was 3-fold up-regulated in MS patients; its possible use as a diagnostic biomarker in PBMCs, plasma and serum was confirmed by ROC-curve analysis (Area under the curve (AUC) 0.785, p = 0.0004; 0.785, p = 0.004; 0.981, P < 0.0001, respectively).
  
  
  CONCLUSIONS
  RRMS patients in remission had altered expression of miRNAs. We validated miR-145 as a potential diagnostic biomarker for the diagnosis of MS in blood, plasma and serum.
authors.affiliation: Department of Neurology, Copenhagen University Hospital Rigshospitalet, Denmark.
authors.forename: Helle Bach
authors.initials: HB
authors.lastname: Søndergaard
authors.forename: Dan
authors.initials: D
authors.lastname: Hesse
authors.forename: Martin
authors.initials: M
authors.lastname: Krakauer
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sørensen
authors.forename: Finn
authors.initials: F
authors.lastname: Sellebjerg
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000276:immunology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D012074:Remission Induction; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005819:Genetic Markers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
keywords: Biomarker; cell types; diagnostics; hematology; interleukin; miRNA; microRNA; multiple sclerosis; relapsing–remitting multiple sclerosis; serological test