title: The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs.
abstract: BACKGROUND
  Gene expression studies of peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE) have demonstrated a type I interferon signature and increased expression of inflammatory cytokine genes. Studies of patients with Aicardi Goutières syndrome, commonly cited as a single gene model for SLE, have suggested that accumulation of non-coding RNAs may drive some of the pathologic gene expression, however, no RNA sequencing studies of SLE patients have been performed. This study was designed to define altered expression of coding and non-coding RNAs and to detect globally altered RNA processing in SLE.
  
  
  METHODS
  Purified monocytes from eight healthy age/gender matched controls and nine SLE patients (with low-moderate disease activity and lack of biologic drug use or immune suppressive treatment) were studied using RNA-seq. Quantitative RT-PCR was used to validate findings. Serum levels of endotoxin were measured by ELISA.
  
  
  RESULTS
  We found that SLE patients had diminished expression of most endogenous retroviruses and small nucleolar RNAs, but exhibited increased expression of pri-miRNAs. Splicing patterns and polyadenylation were significantly altered. In addition, SLE monocytes expressed novel transcripts, an effect that was replicated by LPS treatment of control monocytes. We further identified increased circulating endotoxin in SLE patients.
  
  
  CONCLUSIONS
  Monocytes from SLE patients exhibit globally dysregulated gene expression. The transcriptome is not simply altered by the transcriptional activation of a set of genes, but is qualitatively different in SLE. The identification of novel loci, inducible by LPS, suggests that chronic microbial translocation could contribute to the immunologic dysregulation in SLE, a new potential disease mechanism.
authors.affiliation: The Division of Allergy Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Lihua
authors.initials: L
authors.lastname: Shi
authors.affiliation: The Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Yu
authors.affiliation: Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey, United States of America.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Ehtisham
authors.initials: E
authors.lastname: Akhter
authors.affiliation: The Division of Allergy Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Kelly
authors.initials: K
authors.lastname: Maurer
authors.affiliation: The Division of Allergy Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Costa Reis
authors.affiliation: The Division of Allergy Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.affiliation: The Division of Allergy Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
mesh_terms: D004731:Endotoxins / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D012322:RNA Precursors; D012342:RNA, Small Nuclear / Q000096:biosynthesis*; D059467:Transcriptome
chemical_list: D004731:Endotoxins; D012322:RNA Precursors; D012342:RNA, Small Nuclear