Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome

@article{Hopp2018FootprintsOS,
  title={Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome},
  author={Lydia Hopp and Henry Loeffler-Wirth and Lilit Nersisyan and Arsen Arakelyan and Hans Binder},
  journal={Frontiers in Immunology},
  year={2018},
  volume={9}
}
We analyzed the blood transcriptome of sepsis framed within community-acquired pneumonia (CAP) and characterized its molecular and cellular heterogeneity in terms of functional modules of co-regulated genes with impact for the underlying pathophysiological mechanisms. Our results showed that CAP severity is associated with immune suppression owing to T-cell exhaustion and HLA and chemokine receptor deactivation, endotoxin tolerance, macrophage polarization, and metabolic conversion from… 
Epigenetics of Sepsis
TLDR
This review examines data from in vitro studies, animal studies, and the existing human sepsis studies in epigenetics to demonstrate that epigenetic mechanisms are likely central to the pathogenesis of sepsi and that epigenetics therapies may have potential in the treatment ofsepsis and its associated organ failures.
Epigenetic Regulation in Sepsis, Role in Pathophysiology and Therapeutic Perspective
TLDR
Evidence is strong showing that epigenetic changes, including DNA methylation and post-translational modifications of histones, modulate the inflammatory response of sepsis and the potential of epigenetic interventions for its treatment is shown.
Differential expression of genes associated with T lymphocytes function in septic patients with hypoxemia challenge.
TLDR
Higher illness severity and incidence of lymphopenia was observed following hypoxemia in sepsis and T cell-related gene signatures were associated withHypoxemia during sepsi.
Epigenetic biomarkers for human sepsis and septic shock: insights from immunosuppression.
TLDR
The most relevant epigenetic mechanisms underlying alterations in the innate and adaptive immune responses described in sepsis and septic shock are described, providing several candidates to become epigenetic biomarkers that could improve sepsi management and help predict immunosuppression in postseptic patients.
Genetics in community-acquired pneumonia
TLDR
Delineation of underlying genetic defects and polymorphisms may add in diagnosis, therapy, and prognosis of community-acquired pneumonia.
Sirtuins and Sepsis: Cross Talk between Redox and Epigenetic Pathways
TLDR
The role of sirtuins is reviewed in orchestrating the interplay between the oxidative stress and epigenetic programming during sepsis, a highly conserved family of histone deacetylators and guardians of homeostasis that modulate the immune response in sepsi.
Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia
TLDR
CAP with organ failure showed depressed expression of immunological synapse genes with increased levels of biomarkers denoting endothelial damage, which could help in the early identification of organ failure in CAP and in the implementation of personalized treatment.
DNA methylation of a NF-κB binding site in the aquaporin 5 promoter impacts on mortality in sepsis
TLDR
A functionally important AQP5 promoter cytosine site (nt-937) linked to the binding of the inflammatorily acting nuclear transcription factor NF-κB, with increased methylation in sepsis non-survivors is detected and demonstrates that epigenetic changes impact on sepsi outcome.
Portrayal of the human blood transcriptome of 3,388 adults and its relation to ageing and health
TLDR
A striking overlap of signatures shared by multiple diseases, ageing and obesity driven by an underlying common pattern, which reflects the increase in inflammatory processes is found.
Transcription Factors STAT5A and SPI1 Reveals RHBDD2 as a Potential Biomarker in Sepsis and Septic Shock
TLDR
The identification of the RHBDD2 as a biomarker may facilitate in septic shock diagnosis, treatment, and prognosis.
...
...

References

SHOWING 1-10 OF 111 REFERENCES
Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia
TLDR
It is found that SRS is the major predictor of transcriptomic variation, and a small number of genes were differentially regulated according to the source of infection, enriched for IFN signaling and antigen presentation.
Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study
An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation
Epigenetics As The Driving Force In Long-Term Immunosuppression
TLDR
The literature is reviewed and the most relevant results which explain the epigenetic programs contributing to the progression of sepsis are exposed, including the role of circulating histones in the pathogenesis ofsepsis and septic shock is revisited.
A comprehensive time-course–based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set
Five publicly available gene expression cohorts comparing SIRS/trauma to sepsis were split into time-matched subcohorts and summarized via multicohort analysis, which yielded an 11-gene set that was
Tet2 restrains inflammatory gene expression in macrophages.
Endotoxin tolerance: new mechanisms, molecules and clinical significance.
Transient impairment of reticulocyte hemoglobin content and hepcidin-25 induction in patients with community-acquired pneumonia
TLDR
The hypothesis that hepcidin-25 induces transient impairment of reticulocyte hemoglobin content (Ret-He) is supported as demonstrated in patients with community-acquired pneumonia.
Robust classification of bacterial and viral infections via integrated host gene expression diagnostics
TLDR
An integrated score is created that not only identifies infected patients but also classifies their infection as bacterial or viral, suggesting appropriate treatment, and an integrated antibiotics decision model is built.
...
...