The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs.
<h4>Background</h4>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 syndr...
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Public Library of Science (PLoS)
2014-01-01
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| author | Lihua Shi Zhe Zhang Angela M Yu Wei Wang Zhi Wei Ehtisham Akhter Kelly Maurer Patrícia Costa Reis Li Song Michelle Petri Kathleen E Sullivan |
| author_facet | Lihua Shi Zhe Zhang Angela M Yu Wei Wang Zhi Wei Ehtisham Akhter Kelly Maurer Patrícia Costa Reis Li Song Michelle Petri Kathleen E Sullivan |
| author_sort | Lihua Shi |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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. |
| format | Article |
| id | doaj-art-bb2c653ce9fa455a8ba4b735e59379fb |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-bb2c653ce9fa455a8ba4b735e59379fb2025-08-20T03:01:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9384610.1371/journal.pone.0093846The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs.Lihua ShiZhe ZhangAngela M YuWei WangZhi WeiEhtisham AkhterKelly MaurerPatrícia Costa ReisLi SongMichelle PetriKathleen E Sullivan<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093846&type=printable |
| spellingShingle | Lihua Shi Zhe Zhang Angela M Yu Wei Wang Zhi Wei Ehtisham Akhter Kelly Maurer Patrícia Costa Reis Li Song Michelle Petri Kathleen E Sullivan The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs. PLoS ONE |
| title | The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs. |
| title_full | The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs. |
| title_fullStr | The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs. |
| title_full_unstemmed | The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs. |
| title_short | The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs. |
| title_sort | sle transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non coding and coding rnas |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093846&type=printable |
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