Peripheral blood mononuclear cell transcriptome profiles suggest T-cell immunosuppression after uncomplicated mechanical circulatory support device surgery

Sinha, Ayan; Shahzad, Khurram; Latif, F.; Cadeiras, Martín; Bayern, Manuel Prinz von; Oz, Simin; Naka, Yoshifumi; Deng, Mario C.

doi:10.1016/j.humimm.2009.10.012

Cited by 16 publications

(17 citation statements)

References 19 publications

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“…In our group, efforts to develop prognostic scoring parameters based on leukocyte gene expression profiling are therefore underway. 11 Low albumin is also a marker of poor nutrition and systemic inflammation and is known to be associated with increased mortality in advanced heart failure. 12 In response to the poor outcomes of BIVAD patients, interest is increasing in TAHs as a bridge to transplantation patients with biventricular dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Risk stratification in patients with advanced heart failure requiring biventricular assist device support as a bridge to cardiac transplantation

Cheng

Deng

Tseng

et al. 2012

The Journal of Heart and Lung Transplantation

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Section: Discussionmentioning

confidence: 99%

Risk stratification in patients with advanced heart failure requiring biventricular assist device support as a bridge to cardiac transplantation

Cheng

Deng

Tseng

et al. 2012

The Journal of Heart and Lung Transplantation

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“…Several studies have examined mRNA expression profiles in myocardium after LVAD insertion using gene expression array technology[8-14] and one group studied expression changes in the peripheral blood mononuclear cell transcriptome using microarray technology 24 hours and 7 days following LVAD implant[15]. Nothing is known about how gene expression changes in the peripheral blood of patients after sustained LVAD therapy.…”

Section: Introductionmentioning

confidence: 99%

Identification of Differentially Expressed Transcripts and Pathways in Blood One Week and Six Months Following Implant of Left Ventricular Assist Devices

et al. 2013

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IntroductionContinuous-flow left ventricular assist devices (LVADs) are an established therapy for patients with end-stage heart failure. The short- and long-term impact of these devices on peripheral blood gene expression has not been characterized, and may provide insight into the molecular pathways mediated in response to left ventricular remodeling and an improvement in overall systemic circulation. We performed RNA sequencing to identify genes and pathways influenced by these devices.MethodsRNA was extracted from blood of 9 heart failure patients (8 male) prior to LVAD implantation, and at 7 and 180 days postoperatively. Libraries were sequenced on an Illumina HiSeq2000 and sequences mapped to the human Ensembl GRCh37.67 genome assembly.ResultsA specific set of genes involved in regulating cellular immune response, antigen presentation, and T cell activation and survival were down-regulated 7 days after LVAD placement. 6 months following LVAD placement, the expression levels of these genes were significantly increased; yet importantly, remained significantly lower than age and sex-matched samples from healthy controls.ConclusionsIn summary, this genomic analysis identified a significant decrease in the expression of genes that promote a healthy immune response in patients with heart failure that was partially restored 6 months following LVAD implant.

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“…In previous studies, gene expression profiles of PBMC have been shown to correlate with presence or absence of concurrent acute cellular rejection [16–18, 24], antibody mediated rejection [19], and in response to mechanical circulatory support device implantation [25, 26]. Based on these gene expression profiles, the genomic classifier developed to rule out acute cellular cardiac allograft rejection has also been shown to correlate with different organ function related parameters of rejection [27, 28], and longitudinal changes in clinical profiles [29, 30].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy

Shahzad

Cadeiras

Memon

et al. 2010

Journal of Transplantation

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Background. Cardiac allograft vasculopathy (CAV) is a major cause of graft loss and death after heart transplantation. Currently, no diagnostic methods are available during the early post-transplant period to accurately identify patients at risk of CAV. We hypothesized that PBMC gene expression profiles (GEP) can identify patients at risk of CAV. Methods. We retrospectively analyzed a limited set of whole-genome PBMC microarrays from 10 post-transplant patients who did (n = 3) or did not (n = 7) develop advanced grade CAV during their long-term follow-up. We used significance analysis of microarrays to identify differentially expressed genes and High-Throughput GoMiner to assess gene ontology (GO) categories. We corroborated our findings by retrospective analysis of PBMC real-time PCR data from 33 patients. Results. Over 300 genes were differentially expressed (FDR < 5%), and 18 GO-categories including “macrophage activation”, “Interleukin-6 pathway”, “NF-KappaB cascade”, and “response to virus” were enriched by these genes (FDR < 5%). Out of 8 transcripts available for RT-PCR analysis, we confirmed 6 transcripts (75.0%) including FPRL1, S100A9, CXCL10, PRO1073, and MMP9 (P < .05). Conclusion. Our pilot data suggest that GEP of PBMC may become a valuable tool in the evaluation of patients at risk of CAV. Larger prospectively designed studies are needed to corroborate our hypothesis.

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Peripheral blood mononuclear cell transcriptome profiles suggest T-cell immunosuppression after uncomplicated mechanical circulatory support device surgery

Cited by 16 publications

References 19 publications

Risk stratification in patients with advanced heart failure requiring biventricular assist device support as a bridge to cardiac transplantation

Risk stratification in patients with advanced heart failure requiring biventricular assist device support as a bridge to cardiac transplantation

Identification of Differentially Expressed Transcripts and Pathways in Blood One Week and Six Months Following Implant of Left Ventricular Assist Devices

Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy

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