scholarly journals Current Tolerance-Associated Peripheral Blood Gene Expression Profiles After Liver Transplantation Are Influenced by Immunosuppressive Drugs and Prior Cytomegalovirus Infection

2022 ◽  
Vol 12 ◽  
Author(s):  
Aafke A. Duizendstra ◽  
Michelle V. van der Grift ◽  
Patrick P. Boor ◽  
Lisanne Noordam ◽  
Robert J. de Knegt ◽  
...  

Spontaneous operational tolerance to the allograft develops in a proportion of liver transplant (LTx) recipients weaned off immunosuppressive drugs (IS). Several previous studies have investigated whether peripheral blood gene expression profiles could identify operational tolerance in LTx recipients. However, the reported gene expression profiles differed greatly amongst studies, which could be caused by inadequate matching of clinical parameters of study groups. Therefore, the purpose of this study was to validate differentially expressed immune system related genes described in previous studies that identified tolerant LTx recipients after IS weaning. Blood was collected of tolerant LTx recipients (TOL), a control group of LTx recipients with regular IS regimen (CTRL), a group of LTx recipients with minimal IS regimen (MIN) and healthy controls (HC), and groups were matched on age, sex, primary disease, time after LTx, and cytomegalovirus serostatus after LTx. Quantitative Polymerase Chain Reaction was used to determine expression of twenty selected genes and transcript variants in PBMCs. Several genes were differentially expressed between TOL and CTRL groups, but none of the selected genes were differentially expressed between HC and TOL. Principal component analysis revealed an IS drug dosage effect on the expression profile of these genes. These data suggest that use of IS profoundly affects gene expression in peripheral blood, and that these genes are not associated with operational tolerance. In addition, expression levels of SLAMF7 and NKG7 were affected by prior cytomegalovirus infection in LTx recipients. In conclusion, we found confounding effects of IS regimen and prior cytomegalovirus infection, on peripheral blood expression of several selected genes that were described as tolerance-associated genes by previous studies.

2011 ◽  
Vol 1 (1) ◽  
pp. 12 ◽  
Author(s):  
Soumyaroop Bhattacharya ◽  
Shivraj Tyagi ◽  
Sorachai Srisuma ◽  
Dawn L DeMeo ◽  
Steven D Shapiro ◽  
...  

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11535 ◽  
Author(s):  
Sarah K. Meadows ◽  
Holly K. Dressman ◽  
Pamela Daher ◽  
Heather Himburg ◽  
J. Lauren Russell ◽  
...  

2009 ◽  
Vol 60 (7) ◽  
pp. 2102-2112 ◽  
Author(s):  
Michael G. Barnes ◽  
Alexei A. Grom ◽  
Susan D. Thompson ◽  
Thomas A. Griffin ◽  
Paul Pavlidis ◽  
...  

2018 ◽  
Author(s):  
Slim Fourati ◽  
Aarthi Talla ◽  
Mehrad Mahmoudian ◽  
Joshua G. Burkhart ◽  
Riku Klén ◽  
...  

AbstractRespiratory viruses are highly infectious; however, the variation of individuals’ physiologic responses to viral exposure is poorly understood. Most studies examining molecular predictors of response focus on late stage predictors, typically near the time of peak symptoms. To determine whether pre- or early post-exposure factors could predict response, we conducted a community-based analysis to identify predictors of resilience or susceptibility to several respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV) using peripheral blood gene expression profiles collected from healthy subjects prior to viral exposure, as well as up to 24 hours following exposure. This analysis revealed that it is possible to construct models predictive of symptoms using profiles even prior to viral exposure. Analysis of predictive gene features revealed little overlap among models; however, in aggregate, these genes were enriched for common pathways. Heme Metabolism, the most significantly enriched pathway, was associated with higher risk of developing symptoms following viral exposure.


Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 714
Author(s):  
Heaven L. Roberts ◽  
Massimo Bionaz ◽  
Duo Jiang ◽  
Barbara Doupovec ◽  
Johannes Faas ◽  
...  

We evaluated the effects of a treatment diet contaminated with 1.7 mg deoxynivalenol and 3.5 mg fumonisins (B1, B2 and B3) per kg ration on immune status and peripheral blood gene expression profiles in finishing-stage Angus steers. The mycotoxin treatment diet was fed for a period of 21 days followed by a two-week washout period during which time all animals consumed the control diet. Whole-blood leukocyte differentials were performed weekly throughout the experimental and washout period. Comparative profiles of CD4+ and CD8+ T cells, along with bactericidal capacity of circulating neutrophils and monocytes were evaluated at 0, 7, 14, 21 and 35 days. Peripheral blood gene expression was measured at 0, 7, 21 and 35 days via RNA sequencing. Significant increases in the percentage of CD4-CD8+ T cells were observed in treatment-fed steers after two weeks of treatment and were associated with decreased CD4:CD8 T-cell ratios at this same timepoint (p ≤ 0.10). No significant differences were observed as an effect of treatment in terms of bactericidal capacity at any timepoint. Dietary treatments induced major changes in transcripts associated with endocrine, metabolic and infectious diseases; protein digestion and absorption; and environmental information processing (inhibition of signaling and processing), as evaluated by dynamic impact analysis. DAVID analysis also suggested treatment effects on oxygen transport, extra-cellular signaling, cell membrane structure and immune system function. These results indicate that finishing-stage beef cattle are susceptible to the immunotoxic and transcript-inhibitory effects of deoxynivalenol and fumonisins at levels which may be realistically encountered in feedlot situations.


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