title: Differential microRNA profile and post-transcriptional regulation exist in systemic lupus erythematosus patients with distinct autoantibody specificities.
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) patients have anti-nuclear autoantibodies directed against dsDNA and RNA-associated antigens (extractable nuclear antigens; ENA). In this study, we investigated the differences in microRNA (miRNA) expression and its biological implications in SLE patients with distinct autoantibody specificities.
  
  
  METHODS
  The SLE patients were grouped into three subsets based on the type of autoantibodies present in their sera (anti- ENA+ group with autoantibodies against ENA alone; antidsDNA+ group having autoantibodies against dsDNA only, and anti-ENA+dsDNA+ group having autoantibodies to both dsDNA and ENA). Global miRNA expression profiling was done for each of these three groups using TaqMan® low density miRNA arrays.
  
  
  RESULTS
  We report that different sets of miRNAs are dysregulated in SLE patients with different autoantibody specificities. Further, Ingenuity pathway analysis (IPA) software revealed specific biological pathways that were targeted by miRNAs dysregulated in different SLE subsets. Molecules involved in cell cycle and cytoskeleton remodeling were the prime targets of miRNAs dysregulated in anti-ENA+ patients whereas miRNAs dysregulated in anti-dsDNA+ patients were found to be implicated in multiple cytokine signaling pathways. IPA analysis of gene targets of miRNAs commonly dysregulated in all three SLE subsets identified several metabolic-, hormone-, and interferon-related pathways to be affected.
  
  
  CONCLUSIONS
  The differential miRNA expression in patients with distinct autoantibodies is suggestive of different regulatory mechanisms operating among them. Based on these observations, we are hopeful that this 'sub-grouping' approach could be used to identify other defective processes associated with varying disease manifestations in SLE and may be considered when designing therapeutic interventions.
authors.forename: Sudhir Kumar
authors.initials: SK
authors.lastname: Chauhan
authors.forename: Vikas Vikram
authors.initials: VV
authors.lastname: Singh
authors.forename: Richa
authors.initials: R
authors.lastname: Rai
authors.forename: Madhukar
authors.initials: M
authors.lastname: Rai
authors.forename: Geeta
authors.initials: G
authors.lastname: Rai
mesh_terms: D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000235:genetics*; D000918:Antibody Specificity; D034961:Antigens, Nuclear / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D053263:Gene Regulatory Networks / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D012984:Software
chemical_list: D000974:Antibodies, Antinuclear; D034961:Antigens, Nuclear; D035683:MicroRNAs; D004247:DNA