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Peripheral blood RNA expression profiling in illicit methcathinone users reveals effect on immune system.

ABSTRACT: Methcathinone (ephedrone) is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese), or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We used microarrays to analyze whole-genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data were analyzed by Bayesian modeling and functional annotation. Of 28,869 genes on the microarrays, 326 showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative real-time PCR confirmed differential expression for the most of the genes selected for validation. Functional annotation and network analysis indicated activation of a gene network that included immunological disease, cellular movement, and cardiovascular disease functions (enrichment score 42). As HIV and HCV infections were confounding factors, we performed additional stratification of subjects. A similar functional activation of the "immunological disease" category was evident when we compared subjects according to injection status (past versus current users, balanced for HIV and HCV infection). However, this difference was not large therefore the major effect was related to the HIV status of the subjects. Mn-methcathinone abusers have blood RNA expression patterns that mostly reflect their HIV and HCV infections.

SUBMITTER: Sikk K

PROVIDER: S-EPMC3268596 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Peripheral blood RNA expression profiling in illicit methcathinone users reveals effect on immune system.

Sikk Katrin K Kõks Sulev S Soomets Ursel U Schalkwyk Leonard C LC Fernandes Cathy C Haldre Sulev S Aquilonius Sten-Magnus SM Taba Pille P

Frontiers in genetics 20110819

Methcathinone (ephedrone) is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese), or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We used microarrays to analyze whole-genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data were analyzed by Baye ...[more]

PMID: 22303338

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Project description:OBJECTIVES:The aim of present study was to find genetic pathways activated during infection with bacterial meningitis (BM) and potentially influencing the course of the infection using genome-wide RNA expression profiling combined with pathway analysis and functional annotation of the differential transcription. METHODS:We analyzed 21 patients with BM hospitalized in 2008. The control group consisted of 18 healthy subjects. The RNA was extracted from whole blood, globin mRNA was depleted and gene expression profiling was performed using GeneChip Human Gene 1.0 ST Arrays which can assess the transcription of 28,869 genes. Gene expression profile data were analyzed using Bioconductor packages and Bayesian modeling. Functional annotation of the enriched gene sets was used to define the altered genetic networks. We also analyzed whether gene expression profiles depend on the clinical course and outcome. In order to verify the microarray results, the expression levels of ten functionally relevant genes with high statistical significance (CD177, IL1R2, IL18R1, IL18RAP, OLFM4, TLR5, CPA3, FCER1A, IL5RA, and IL7R) were confirmed by quantitative real-time (qRT) PCR. RESULTS:There were 8569 genes displaying differential expression at a significance level of p < 0.05. Following False Discovery Rate (FDR) correction, a total of 5500 genes remained significant at a p-value of < 0.01. Quantitative RT-PCR confirmed the differential expression in 10 selected genes. Functional annotation and network analysis indicated that most of the genes were related to activation of humoral and cellular immune responses (enrichment score 43). Those changes were found in both adults and in children with BM compared to the healthy controls. The gene expression profiles did not significantly depend on the clinical outcome, but there was a strong influence of the specific type of pathogen underlying BM. CONCLUSION:This study demonstrates that there is a very strong activation of immune response at the transcriptional level during BM and that the type of pathogen influences this transcriptional activation.

Project description:BACKGROUND: Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix® GeneChip® Bovine Genome Array with 24,072 gene probe sets representing more than 23,000 gene transcripts. RESULTS: Control and infected animals had similar mean white blood cell counts. However, the mean number of lymphocytes was significantly increased in the infected group relative to the control group (P = 0.001), while the mean number of monocytes was significantly decreased in the BTB group (P = 0.002). Hierarchical clustering analysis using gene expression data from all 5,388 detectable mRNA transcripts unambiguously partitioned the animals according to their disease status. In total, 2,960 gene transcripts were differentially expressed (DE) between the infected and control animal groups (adjusted P-value threshold ? 0.05); with the number of gene transcripts showing decreased relative expression (1,563) exceeding those displaying increased relative expression (1,397). Systems analysis using the Ingenuity® Systems Pathway Analysis (IPA) Knowledge Base revealed an over-representation of DE genes involved in the immune response functional category. More specifically, 64.5% of genes in the affects immune response subcategory displayed decreased relative expression levels in the infected animals compared to the control group. CONCLUSIONS: This study demonstrates that genome-wide transcriptional profiling of PBL can distinguish active M. bovis-infected animals from control non-infected animals. Furthermore, the results obtained support previous investigations demonstrating that mycobacterial infection is associated with host transcriptional suppression. These data support the use of transcriptomic technologies to enable the identification of robust, reliable transcriptional markers of active M. bovis infection.

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Peripheral blood RNA expression profiling in illicit methcathinone users reveals effect on immune system.

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Peripheral blood RNA expression profiling in illicit methcathinone users reveals effect on immune system.

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