scholarly journals A Whole Blood Transcriptome Signature Implicates Dysregulation of Both Innate and Adaptive Immunity in Septic Shock

2021 ◽  
Author(s):  
H.M. Giannini ◽  
C.V. Cosgriff ◽  
X.M. Lu ◽  
B.J. Anderson ◽  
T.K. Jones ◽  
...  
Keyword(s):  
Septic Shock ◽  
Adaptive Immunity ◽  
Whole Blood ◽  
Innate And Adaptive Immunity ◽  
Transcriptome Signature ◽  
Blood Transcriptome

scholarly journals Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration

BMC Genomics ◽  
2017 ◽  
Vol 18 (S8) ◽  
Author(s):  
Guan Wang ◽  
Jérôme Durussel ◽  
Jonathan Shurlock ◽  
Martin Mooses ◽  
Noriyuki Fuku ◽  
...  
Keyword(s):  
Whole Blood ◽  
Recombinant Human Erythropoietin ◽  
Human Erythropoietin ◽  
Transcriptome Signature ◽  
Blood Transcriptome

scholarly journals Transcriptomic Profiles in Children With Septic Shock With or Without Immunoparalysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Andrew Snyder ◽  
Kathleen Jedreski ◽  
James Fitch ◽  
Saranga Wijeratne ◽  
Amy Wetzel ◽  
...  
Keyword(s):  
Septic Shock ◽  
Natural Killer ◽  
Adaptive Immunity ◽  
Expression Patterns ◽  
Killer Cell ◽  
Patient Specific ◽  
Cell Mediated Immunity ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

BackgroundSevere innate immune suppression, termed immunoparalysis, is associated with increased risks of nosocomial infection and mortality in children with septic shock. Currently, immunoparalysis cannot be clinically diagnosed in children, and mechanisms remain unclear. Transcriptomic studies identify subsets of septic children with downregulation of genes within adaptive immune pathways, but assays of immune function have not been performed as part of these studies, and little is known about transcriptomic profiles of children with immunoparalysis.MethodsWe performed a nested case-control study to identify differences in RNA expression patterns between children with septic shock with immunoparalysis (defined as lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)α response < 200 pg/ml) vs those with normal LPS-induced TNFα response. Children were enrolled within 48 hours of the onset of septic shock and divided into two groups based on LPS-induced TNFα response. RNA was extracted from whole blood for RNAseq, differential expression analyses using DESeq2 software, and pathway analyses using Ingenuity Pathway Analysis.Results32 children were included in analyses. Comparing those with immunoparalysis (n =19) to those with normal TNFα response (n = 13), 2,303 transcripts were differentially expressed with absolute value fold change ≥ 1.5 and false discovery rate ≤ 0.05. The majority of downregulated pathways in children with immunoparalysis were pathways that involved interactions between innate and adaptive immune cells necessary for cell-mediated immunity, crosstalk between dendritic cells and natural killer cells, and natural killer cell signaling pathways. Upregulated pathways included those involved in humoral immunity (T helper cell type 2), corticotropin signaling, platelet activation (GP6 signaling), and leukocyte migration and extravasation.ConclusionsOur study suggests that gene expression data might be useful to identify children with immunoparalysis and identifies several key differentially regulated pathways involved in both innate and adaptive immunity. Our ongoing work in this area aims to dissect interactions between innate and adaptive immunity in septic children and to more fully elucidate patient-specific immunologic pathophysiology to guide individualized immunotherapeutic targets.

scholarly journals Associations of cells from both innate and adaptive immunity with lower nerve conduction velocity: the Maastricht Study

2021 ◽  
Vol 9 (1) ◽  
pp. e001698
Author(s):  
Haifa Maalmi ◽  
Kristiaan Wouters ◽  
Hans H C M Savelberg ◽  
Jeroen H P M van der Velde ◽  
Jos P H Reulen ◽  
...  
Keyword(s):  
T Cells ◽  
Adaptive Immunity ◽  
Conduction Velocity ◽  
Nerve Conduction ◽  
Nerve Conduction Velocity ◽  
Essential Feature ◽  
Sensory Nerve ◽  
Linear Regression Models ◽  
Cross Sectional ◽  
Innate And Adaptive Immunity

IntroductionDistal sensorimotor polyneuropathy (DSPN) is common in people with diabetes but is also found in pre-diabetes. Peripheral nerve myelin damage, which can be assessed by reduced nerve conduction velocity (NCV), is an essential feature of DSPN. Emerging evidence indicates that the development of DSPN may involve the activation of the immune system. However, available studies have mainly investigated circulating immune mediators, whereas the role of immune cells remains unclear. Therefore, we aimed to test whether leukocyte subsets are associated with NCV.Research design and methodsThis cross-sectional study analyzed data from 850 individuals (of whom 252 and 118 had type 2 diabetes and pre-diabetes, respectively) of the Maastricht Study. NCV was measured in the peroneal and tibial motor nerves and the sural sensory nerve and summed to calculate a standardized NCV sum score. Associations between percentages of leukocyte subsets and NCV sum scores were estimated using linear regression models adjusted for demographic, lifestyle, metabolic and clinical covariates.ResultsAfter adjustment for covariates, higher percentages of basophils and CD4+ T cells were associated with lower NCV (p=0.014 and p=0.005, respectively). The percentage of CD8+ T cells was positively associated with NCV (p=0.022). These associations were not modified by glucose metabolism status (all pinteraction >0.05). No associations were found for monocytes, eosinophils, neutrophils, lymphocytes, total T cells, Treg cells and B cells.ConclusionsThe associations of basophils, CD4+ and CD8+ T cells with NCV suggest that cell types from both innate and adaptive immunity may be implicated in the development of DSPN.

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