Gut microbiota analysis in poorly controlled diabetes patients with latent TB infection (LTBI) and nonLTBI [16S rRNA]
Ontology highlight
ABSTRACT:
ORGANISM(S): human feces metagenome
PROVIDER: GSE199810 | GEO | 2023/01/18
REPOSITORIES: GEO
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Project description:In latent tuberculosis infection (LTBI) spread of the bacteria is contained by a persistent immune response, which includes CD4+ T cells as important contributors. Here we show that TB-specific CD4+ T cells have a characteristic chemokine expression signature (CXCR3+CCR6+CCR4-; Th* cells), and that the overall number of Th* cells is significantly increased in LTBI donors. We have comprehensively characterized the transcriptional signature of Th* cells and find significant differences to conventional Th1, Th17 and Th2 cells, but no major changes between healthy and LTBI donors. Th* cells display linage-specific signatures of both Th1 and Th17 cells, but also have a unique gene expression program including genes associated with susceptibility to TB, enhanced T cell activation, enhanced cell survival, and induction of a cytotoxic program akin to CTL cells. Overall, the gene expression signature of Th* reveals characteristics of cells important in controlling latent infections.
2014-07-18 | GSE56179 | GEO
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in two African adult populations. Transcriptional signatures were identified that distinguished active TB from LTBI, active TB from other diseases, and active TB from both LTBI and other diseases in HIV+/- patients.
2013-10-23 | GSE37250 | GEO
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in two African adult populations. Transcriptional signatures were identified that distinguished active TB from LTBI, active TB from other diseases, and active TB from both LTBI and other diseases in HIV+/- patients. Adults were recruited from Cape Town, South Africa (n=300) and Karonga, Malawi (n=237) who were either HIV+ or HIV - with either active TB, LTBI or OD. Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 Beadchips. Data were analysed in R.
2013-10-23 | E-GEOD-37250 | biostudies-arrayexpress
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in a paediatric cohort from Kenya Transcriptional signatures were identified that distinguished active TB from LTBI, active TB from other diseases, and active TB from both LTBI and other diseases in HIV+/- patients.
2014-05-01 | GSE39939 | GEO
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in a paediatric cohort from Kenya Transcriptional signatures were identified that distinguished active TB from LTBI, active TB from other diseases, and active TB from both LTBI and other diseases in HIV+/- patients. Children were recruited from 2 hospitals in Coast Province, Kenya (n=157) who were either HIV+ or HIV - with either active TB (culture confirmed), active TB (culture negative), LTBI or OD. Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 Beadchips. Data were analysed in R.
2014-05-01 | E-GEOD-39939 | biostudies-arrayexpress
Project description:While blood transcriptional profiling has improved diagnosis and understanding of disease pathogenesis of adult tuberculosis (TB), no studies applying gene expression profiling of children with TB have been described so far. In this study, we have compared whole blood gene expression in childhood TB patients, as well as in healthy latently infected (LTBI) and uninfected (HC) children in a cohort of Warao Amerindians in the Delta Amacuro in Venezuela. We identified a 116-gene signature set by means of random forest analysis that showed an average prediction error of 11% for TB vs. LTBI and for TB vs. LTBI vs. HC in our dataset. Furthermore, a minimal set of only 9 genes showed a significant predictive value for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. Additionally, a minimal gene set of 42 genes with a comparable predictive value to the 116-gene set in both our dataset and the previously published literature cohorts for the comparsion of TB vs. LTBI vs. HC was identified. In order to identify a robust representative gene set that would hold stand among different ethnic populations, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these ten genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to diagnose 78% of the TB cases correctly with 100% specificity. We conclude that our data justify the further exploration of our signature set as biomarkers to diagnose childhood TB. Furthermore, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts. In this study, 27 children 1 to 15 years of age with TB (n=9), LTBI (n=9) and HC (n=9) were recruited between May 2010 and December 2010. Tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assay (QFT-GIT) were performed on all children. A sputum sample was collected from all children with expectoration and a gastric aspirate was taken from all children under 6 years of age. Children with active TB were diagnosed based on culture of M. tuberculosis (n=2) or on the basis of clinical, epidemiological and radiological features (n=7). The latter group were children with a TST = 10 mm or a positive QFT-GIT result who presented all of: persistent fever >38M-BM-0C objectively recorded daily for at least two weeks, persistent cough for more than three weeks, weight loss (>5% reduction in weight compared with the highest weight recorded in last three months) or failure to thrive (documented crossing of percentile lines in the preceding three months), persistent lethargy or decrease in playfulness/activity reported by the parent and absence of clinical response on broad-spectrum antibiotics. Standard antero-posterior and lateral chest radiographs (CXRs) were taken from all children. Two independent experts, blinded to all clinical information, evaluated the CXRs and documented their findings on a standard report form. Where the two objective experts disagreed, a third expert was consulted and final consensus was achieved. A diagnosis of TB was only made when the CXR was consistent with TB9 and the child showed a positive clinical response to anti-TB treatment. Children were followed up clinically, radiologically and, in case of a negative TST at inclusion, by means of TST at six and 12 months after inclusion. LTBI was defined as a TST = 10mm and a positive QFT-GIT with a negative culture result on inclusion in the absence of radiological and clinical evidence of TB disease on inclusion as well as on t=6 and t=12 months. HC were children with a TST = 0 mm at inclusion and at t=6 and t=12 months. The HC had a negative QFT-GIT and a negative culture result at inclusion without radiological or clinical evidence of TB disease on inclusion nor on t=6 and t=12 months. TB patients were sampled before initiation of anti-TB treatment. Of three of the nine TB patients, a follow-up sample was taken when the patient was in anti-TB treatment for five months. All children were HIV-negative. 27 samples in total where analyzed, active TB infection (TB, n=9), Latent TB infection (LTBI, n=9) and healthy controls (HC, n=9) . Gene expression values were log2-transformed and differentially expressed genes were identified based on log2 fold changes (M-values). P values were calculated with a Bayes-regularized one-way ANOVA. Random Forest recursive feature elimination was used to find a signature geneset capable of discrimination active TB from latent TB and from non-infected individuals.
2013-02-05 | E-GEOD-41055 | biostudies-arrayexpress
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in two African paediatric populations. Transcriptional signatures were identified that distinguished active TB from LTBI, and active TB from other diseases. Children were recruited from Cape Town, South Africa (n=157) and Blantyre, Malawi (n=177) who were either HIV+ or HIV - with either active TB, LTBI or OD. Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 Beadchips. Data were analysed in R.
2014-05-01 | E-GEOD-39940 | biostudies-arrayexpress
Project description:While blood transcriptional profiling has improved diagnosis and understanding of disease pathogenesis of adult tuberculosis (TB), no studies applying gene expression profiling of children with TB have been described so far. In this study, we have compared whole blood gene expression in childhood TB patients, as well as in healthy latently infected (LTBI) and uninfected (HC) children in a cohort of Warao Amerindians in the Delta Amacuro in Venezuela. We identified a 116-gene signature set by means of random forest analysis that showed an average prediction error of 11% for TB vs. LTBI and for TB vs. LTBI vs. HC in our dataset. Furthermore, a minimal set of only 9 genes showed a significant predictive value for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. Additionally, a minimal gene set of 42 genes with a comparable predictive value to the 116-gene set in both our dataset and the previously published literature cohorts for the comparsion of TB vs. LTBI vs. HC was identified. In order to identify a robust representative gene set that would hold stand among different ethnic populations, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these ten genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to diagnose 78% of the TB cases correctly with 100% specificity. We conclude that our data justify the further exploration of our signature set as biomarkers to diagnose childhood TB. Furthermore, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts. In this study, 27 children 1 to 15 years of age with TB (n=9), LTBI (n=9) and HC (n=9) were recruited between May 2010 and December 2010. Tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assay (QFT-GIT) were performed on all children. A sputum sample was collected from all children with expectoration and a gastric aspirate was taken from all children under 6 years of age. Children with active TB were diagnosed based on culture of M. tuberculosis (n=2) or on the basis of clinical, epidemiological and radiological features (n=7). The latter group were children with a TST = 10 mm or a positive QFT-GIT result who presented all of: persistent fever >38°C objectively recorded daily for at least two weeks, persistent cough for more than three weeks, weight loss (>5% reduction in weight compared with the highest weight recorded in last three months) or failure to thrive (documented crossing of percentile lines in the preceding three months), persistent lethargy or decrease in playfulness/activity reported by the parent and absence of clinical response on broad-spectrum antibiotics. Standard antero-posterior and lateral chest radiographs (CXRs) were taken from all children. Two independent experts, blinded to all clinical information, evaluated the CXRs and documented their findings on a standard report form. Where the two objective experts disagreed, a third expert was consulted and final consensus was achieved. A diagnosis of TB was only made when the CXR was consistent with TB9 and the child showed a positive clinical response to anti-TB treatment. Children were followed up clinically, radiologically and, in case of a negative TST at inclusion, by means of TST at six and 12 months after inclusion. LTBI was defined as a TST = 10mm and a positive QFT-GIT with a negative culture result on inclusion in the absence of radiological and clinical evidence of TB disease on inclusion as well as on t=6 and t=12 months. HC were children with a TST = 0 mm at inclusion and at t=6 and t=12 months. The HC had a negative QFT-GIT and a negative culture result at inclusion without radiological or clinical evidence of TB disease on inclusion nor on t=6 and t=12 months. TB patients were sampled before initiation of anti-TB treatment. Of three of the nine TB patients, a follow-up sample was taken when the patient was in anti-TB treatment for five months. All children were HIV-negative.
2013-02-05 | GSE41055 | GEO
Project description:We applied a cell population transcriptomics strategy to sorted human memory CD8 T cells to define novel immune signatures of latent tuberculosis infection (LTBI) and understand the phenotype of tuberculosis (TB)-specific T cells. We found a 41-gene signature that could discriminate between memory CD8 T cells from healthy LTBI subjects and noninfected controls. The gene signature was dominated by genes known to be associated with mucosal associated invariant T cells (MAITs) and reflected the lower frequency of MAITs observed in individuals with LTBI. There was no evidence for a conventional CD8 T cell specific signature between the two cohorts. We therefore investigated the MAITs in more detail in these cohorts. Phenotyping based on Vα7.2 and CD161 expression and MR1 tetramers revealed 2 distinct populations of CD8+Vα7.2+CD161+ T cells: MR1 tetramer+ and MR1 tetramer−, both of which had a distinct gene expression profile compared to CD8 memory T cells. Transcriptomic analysis of LTBI vs. noninfected individuals did not reveal significant differences for MR1 tetramer+ cells. However, gene expression of MR1 tetramer− cells showed a very different profile with large inter-individual diversity and a TB-specific signature. This was further strengthened by a more diverse TCR-α and -β repertoire of MR1 tetramer− cells as compared to MR1 tetramer+. Thus, cell population transcriptomics revealed a dominant MAIT signature in CD8 memory T cells that upon detailed investigation provided novel insights into the phenotype of different MAIT populations implicated in tuberculosis.
2020-05-13 | GSE132790 | GEO
Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in two African paediatric populations. Transcriptional signatures were identified that distinguished active TB from LTBI, and active TB from other diseases.
2014-05-01 | GSE39940 | GEO