Genome-Wide Expression Profiling Identifies Type 1 Interferon Response Pathways in Active Tuberculosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE56153 | GEO | 2014/03/25
SECONDARY ACCESSION(S): PRJNA242560
REPOSITORIES: GEO
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Project description:Whole-genome expression profiling on a cohort of TB patients. Tuberculosis patients above 15 years of age were recruited from an outpatient tuberculosis clinic in central Jakarta (Indonesia). Randomly selected control subjects with the same sex and age (+/-10%) were recruited from neighboring households, with first degree relatives excluded. Total RNA obtained from human whole blood of TB patients longitudinally sampled along 3 time-points: during active infection, during treatment, and after completion of curative treatment
2014-03-25 | E-GEOD-56153 | biostudies-arrayexpress
Project description:Blood transcriptional signatures may discriminate individuals with tuberculosis (TB) from disease-free controls, or from patients with other infectious or respiratory diseases. To systematically evaluate the diagnostic accuracy of published transcriptional signatures in a clinically relevant population with high burden of TB and human immunodeficiency virus (HIV), adults presenting for investigation of possible pulmonary TB were consecutively recruited at a TB clinic in South Africa. At enrolment, peripheral blood was collected in Tempus tubes (for RNA sequencing) and patients provided two sputum samples (for Xpert and liquid culture). Amongst 181 patients (median age 35 years), 44 (24%) were infected with human immunodeficiency virus (HIV). 54 patients (30%) were diagnosed with Xpert- or culture-positive TB. No alternate diagnoses were available for Xpert- and culture-negative non-TB patients.
2020-03-17 | E-MTAB-8290 | biostudies-arrayexpress
Project description:To study the transcriptional profile of patients with acute RSV or Influenza infection,children of median age 2.4 months (range 1.5-8.6) hospitalized with acute RSV and influenza virus infection were offered study enrollment after microbiologic confirmation of the diagnosis. Blood samples were collected from them within 42-72 hours of hospitalization. We excluded children with suspected or proven polymicrobial infections, with underlying chronic medical conditions (i.e congenital heart disease, renal insufficiency), with immunodeficiency, or those who received systemic steroids or other immunomodulatory therapies. The RSV cohort consisted of 51 patients with median age of 2 months (range 1.5-3.9) and the influenza cohort had 28 patients with median age of 5.5 months (range 1.4-21). Control samples were obtained from healthy children undergoing elective surgical procedures or at outpatient clinic visits. To exclude viral co-infections we performed nasopharyngeal viral cultures of all subjects. We recruited 10 control patients for the RSV cohort with median age of 6.7 months (range 5-10), and 12 control patients for the influenza cohort with median age of18.5 months (range 10.5-26).
2012-03-12 | GSE34205 | GEO
Project description:To study the transcriptional profile of patients with acute RSV or Influenza infection,children of median age 2.4 months (range 1.5-8.6) hospitalized with acute RSV and influenza virus infection were offered study enrollment after microbiologic confirmation of the diagnosis. Blood samples were collected from them within 42-72 hours of hospitalization. We excluded children with suspected or proven polymicrobial infections, with underlying chronic medical conditions (i.e congenital heart disease, renal insufficiency), with immunodeficiency, or those who received systemic steroids or other immunomodulatory therapies. The RSV cohort consisted of 51 patients with median age of 2 months (range 1.5-3.9) and the influenza cohort had 28 patients with median age of 5.5 months (range 1.4-21). Control samples were obtained from healthy children undergoing elective surgical procedures or at outpatient clinic visits. To exclude viral co-infections we performed nasopharyngeal viral cultures of all subjects. We recruited 10 control patients for the RSV cohort with median age of 6.7 months (range 5-10), and 12 control patients for the influenza cohort with median age of18.5 months (range 10.5-26). We used microarrays to obtain the transcriptional profile of PBMCs from patients with acute RSV or Influenza infection and compared these signatures with the transcriptional profile of primary airway epithelial cells infected with RSV or Influenza.
2012-03-12 | E-GEOD-34205 | biostudies-arrayexpress
Project description:People with diabetes are more likely to develop tuberculosis (TB) and to have poor TB treatment outcomes than those without. We previously showed that blood transcriptomes in people with TB-diabetes (TB-DM) co-morbidity have excessive inflammatory and reduced interferon responses at TB diagnosis. It is unknown whether this persists through treatment, potentially underlying adverse outcomes. Methods Pulmonary TB patients were recruited in South Africa, Indonesia and Romania, and classified as having TB-DM, TB with prediabetes, TB-related hyperglycaemia or uncomplicated TB, based on glycated haemoglobin (HbA1c) concentration at TB diagnosis and after 6 months of TB treatment. Gene expression in blood samples collected at diagnosis and at regular intervals throughout treatment was measured by unbiased RNA-Seq and targeted Multiplex Ligation-dependent Probe Amplification. Results Gene expression was modulated by TB treatment in all groups but to different extents, such that differences remained in people with TB-DM relative to TB-only throughout, including genes involved in innate responses, anti-microbial immunity and the inflammasome. People with prediabetes or with TB-related hyperglycaemia had gene expression more similar to people with TB-DM than TB-only throughout treatment. The overall pattern of change was similar across clinical groups irrespective of glycaemic index, permitting models predictive of TB treatment to be developed. Conclusions The exacerbated transcriptome changes seen in TB-DM take longer to resolve during TB treatment, indicating that prolonged treatment or host-directed therapy may be needed to improve TB treatment outcomes. Development of transcriptome-based biomarker signatures of TB-treatment response should include people with diabetes to be useful across populations.
2023-09-05 | GSE193978 | GEO
Project description:Analysis of transcriptional differences between HIV infected persons with evidence of latent tuberculosis (TB) infection by Quantiferon Gold-in-tube, with and without evidence of subclinical TB disease on FDG-PET/CT scan. Tuberculosis is classically divided into two clinical states: latent infection and active disease. One-quarter of the global population is considered latently infected but diagnostic tests poorly predict the small proportion that will progress to disease. We recruited 35 asymptomatic, HIV-1 infected adults with latent TB by current diagnostic criteria, who underwent [18F]-fluoro-2-deoxy-D-glucose positron emission/computed tomography; ten had pulmonary abnormalities consistent with subclinical disease and were significantly more likely to progress. As positive control, we recruited 15 HIV-1 infected adults with symptomatic microbiologically confirmed active pulmonary TB, age, sex and CD4 matched to the 35 participants undergoing FDG-PET/CT. By whole-blood transcriptomic profiling we characterised 82-transcripts distinguishing those with subclinical pathology from those without. Transcripts representing the classical complement pathway were overabundant in both subclinical and active TB. We have demonstrated that latent TB is not a homogenous condition and defined a distinct high-risk subgroup with evidence of subclinical disease. These findings point the way to the future development of more predictive diagnostic tests.
2018-01-01 | GSE69581 | GEO
Project description:The aim of this study was to compare the transcriptional response to TB in regions of different incidence / prevalence. Experimental Design: Whole blood collected in tempus tubes from patients with different spectra of TB disease. All patients were sampled prior to the initiation of any antimycobacterial therapy. Active Pulmonary TB: PTB - All patients confirmed by isolation of Mycobacterium Tuberculosis on culture of sputum. Latent TB: LTB - All patients were screened at a tuberculosis clinic. All were positive by Interferon-Gamma Release assay(IGRA); specifically Quantiferon Gold In-Tube Assay (Cellestis, Australia). Latent patients had no clinical, or microbiological evidence of active infection and were asymptomatic. Experimental Variables: Patient group: Active PTB; Latent TB. There are no healthy controls in this dataset as it was being used for validation only. Controls: Latent TB individuals are used as a control for PTB in this dataset since there are few to no unexposed adult controls in Cape Town.
2010-08-11 | E-GEOD-19442 | biostudies-arrayexpress
Project description:Blood transcriptional signatures may predate clinical diagnosis and detect subclinical incipient tuberculosis (TB) disease. To validate such blood signatures, close contacts of TB patients were recruited from multiple TB clinics in London. Close contacts of active TB were defined as individuals with a cumulative duration of exposure of greater than eight hours in a confined space to the index case prior to initiation of treatment. Known human immunodeficiency virus (HIV)-positive patients were excluded. At enrolment, interferon gamma release assays (IGRAs) were done using the QuantiFERON-TB Plus assay (Qiagen, Germany), and peripheral blood was collected into Tempus tubes for whole genome transcriptional profiling by RNA sequencing. Participants who progressed to active TB were identified by linkage with the national electronic TB register. Local case notes were reviewed to identify individuals who had received preventative treatment. This submission contains data from n=360 adult participants, of which n=9 progressed to TB during a median follow-up time of 1.9 years. The data were used for two publications: The first publication (Roe et al 2019) makes use of an initial subset of n=333 participants, of which n=6 progressed to TB during the median follow-up time of 346 days. In the second publication (Gupta et al 2019), we extended the dataset to n=360 participants and the median follow-up time to 1.9 years; n=3 initial non-progressors progressed to TB during this extended follow-up.
2019-08-29 | E-MTAB-6845 | biostudies-arrayexpress
Project description:Understanding the immune response to tuberculosis requires greater knowledge of humoral responses. To characterize antibody targets and the effect of disease parameters on target recognition, we developed a systems immunology approach that integrated detection of antibodies against the entire Mycobacterium tuberculosis proteome, bacterial metabolic and regulatory pathway information, and patient data. Probing ~4,000 M. tuberculosis proteins with sera from >500 suspected tuberculosis patients worldwide revealed that antibody responses recognized ~10% of the bacterial proteome. This result defines the immunoproteome of M. tuberculosis, which is rich in membrane-associated and extracellular proteins. Most serum reactivity during active tuberculosis focused onto ~0.5% of the proteome. Within this pool, which is selectively enriched for extracellular proteins (but not for membrane-associated proteins), relative target preference varied among patients. The shift in relative M. tuberculosis protein reactivity observed with active tuberculosis defines the evolution of the humoral immune response during M. tuberculosis infection and disease. Peripheral blood was collected from prospectively enrolled TB suspects among subjects seeking care for pulmonary symptoms at clinics associated with national TB control programs in 11 countries. M. tuberculosis proteome microarrays representing 4099 bacterial protein spots were probed with sera from 561 TB suspects. Based on the final diagnosis, they belonged to two classes: TB (n=254) and Non-TB Disease (n=307). In addition, healthy individuals negative to Latent TB Infection (LTBI neg, n=64) were also tested (negative control sera). Each serum was tested with a single array and no replicate experiments were performed. The reactivity of a serum to an M. tuberculosis protein (reactivity call) was defined based on the distribution of negative control sera intensity for that protein using Z-statistics. Based on the distribution of reactivity calls, 27 outlier samples reacting with more than 20 proteins were excluded from further analysis. The association of reactivity calls of each protein with TB/NTBD status of TB suspects was determined by estimating odds ratio and 95% confidence interval.
2010-07-13 | E-GEOD-19433 | biostudies-arrayexpress
Project description:Human infection with Mycobacterium tuberculosis results in a continuum of ill-defined, clinical manifestations with stable latent M. tuberculosis infection (LTBI) and severe active disease at the ends. Identifying different states of infection is of importance to tuberculosis (TB) control since risk of developing active disease varies among different asymptomatic states while infectiousness varies among patients with different bacterial burden. We investigated changes in proteome-scale antibody responses during disease progression in a non-human primate model of tuberculosis. We probed M. tuberculosis proteome microarrays with serial sera collected from three infection-outcome groups (active, reactivation, and latent). We found that each infection outcome is associated with characteristic changes in the antibody levels and number of antigenic targets, which suggested an association between antibody responses and bacillary burden. Additional proteome-scale serological profiling of > 400 human TB suspects established that antibody responses are positively associated with bacterial load. Thus tuberculosis-specific antibody levels and number of antigenic targets increases with disease progression. Serum samples collected from adult patients with suspected tuberculosis during a multi-site study was used to probe whole proteome microarrays. Subject recruitment was conducted under uniform protocols approved by the institutional ethics committee at each site. Final diagnosis of active TB was based on positive M. tuberculosis culture results. The active TB patients were further subdivided into smear-positive and negative disease based on results of Ziehl-Neelsen staining of sputum smears for acid fast bacilli. Active TB was excluded as a diagnosis (Non-TB Disease [NTBD] patients) based on having negative M. tuberculosis culture and smear results and on having an alternate diagnosis. All subjects were presumably negative for HIV infection given the very low incidence of HIV infection in the study sites. Sera from 169 TB and 242 NTBD patients were selected for microarray probing. The control sera (n = 14) which was used to generate negative control distribution for each protein were negative to latent M. tuberculosis infection, as indicated by negative results to tuberculin skin test.
2012-07-05 | E-GEOD-30722 | biostudies-arrayexpress