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| Status |
Public on Mar 30, 2020 |
| Title |
Modulation of LTR-retrotransposons expression in mHLA-DR stratified septic shock patients: a pilot study [IS] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Background: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. To date, no biomarker has shown sufficient evidence and ease of application in clinical routine to monitor the complexity of the sepsis-related immune alterations. Multiple levels of interaction of human endogenous retroviruses (HERVs) with the immune response led us to hypothesize that they may be relevant candidates both to contribute to the physiopathology of sepsis and to be part of a molecular signature. In this study, we used a recently described high-density microarray which allows exploring HERVs/MaLRs transcriptome in septic shock patients.
Results: About 6.9% of the HERVs/MalRs repertoire is transcribed in whole blood. Concerning the functionality of LTRs, the majority of LTRs are silent (62.9%), 7.5% of LTRs present a putative constitutive promoter or polyA functions, while 20.4% of them may shift from silent to active. Evidence was given that a subset of HERVs/MaLRs and genes were modulated in septic shock patients according to the monocyte HLA-DR (mHLA-DR) expression level measured by flow cytometry, as a proxy of immunosuppression. We then identified a large signature consisting of 193 differentially expressed HERVs/MaLRs probesets further reduced to a smaller 10 HERVs/MaLRs signature. Both signatures, validated in an independent septic shock cohort, identified two groups of patients with different severity features including clinical criteria and the CD74 and CX3CR1 sepsis severity molecular markers.
Conclusion: This microarray-based approach unveiled the expression of about 87,912 distinct HERV probesets and identified 764 putative promoter LTRs and 642 putative polyA LTRs in whole blood. HERV/MaLR expression was shown to be tightly modulated in septic shock patients according to mHLA-DR expression. We identified a set of potential molecular biomarkers in septic shock patients partially overlapping immunosuppression (mHLA-DR), and the risk of Health Care associated Infections (HAI) (CD74 ratio), complementary to existing molecular markers of a sepsis patients stratification. We identified a HERV/MaLR signature discriminating patients based on their immunosuppression state and severity.
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| Overall design |
10 septic shock patients at D1 and D3-4 after ICU admission presenting with features of sepsis-induced immunosuppression or not (HLA-DR low/high), and compared to 4 healthy controls
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| Contributor(s) |
Mommert M, Tabone O, Guichard A, Oriol G, Cerrato E, Denizot M, Pachot A, Lepape A, Monneret G, Venet F, Brengel-Pesce K, Textoris J, Mallet F |
| Citation(s) |
32188504 |
| |
| Submission date |
Oct 16, 2018 |
| Last update date |
Mar 30, 2020 |
| Contact name |
Julien Textoris |
| E-mail(s) |
julien.textoris@gmail.com
|
| Phone |
+33 472 119 546
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| Organization name |
bioMérieux
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| Department |
Medical Diagnostic Discovery Department (MD3)
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| Lab |
Joint Research Unit - bioMérieux / HCL
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| Street address |
Hôpital Edouard herriot - Pavillon P; 5 place d'Arsonval
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| City |
Lyon |
| ZIP/Postal code |
69437 |
| Country |
France |
| |
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| Platforms (1) |
| GPL22462 |
[bMxHERV3b520850] Affymetrix HERVV3 Array |
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| Samples (44)
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| This SubSeries is part of SuperSeries: |
| GSE121352 |
Modulation of LTR-retrotransposons expression in mHLA-DR stratified septic shock patients: a pilot study |
|
| Relations |
| BioProject |
PRJNA497116 |
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