Immunogenetics of blood biomarkers & pediatric tuberculosis
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ABSTRACT:
PROVIDER: PRJNA1036359 | ENA |
REPOSITORIES: ENA
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Project description:Immunogenetics of BCG Vaccination & Pediatric Tuberculosis
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Project description:Immunogenetics of BCG Vaccination & Pediatric Tuberculosis
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Project description:Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic in the context of house hold contacts.
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Project description:Identification of blood biomarkers that prospectively predict Mycobacterium tuberculosis treatment response.
2017-11-01 | GSE89403 | GEO
Project description:Background Pediatric tuberculosis (TB) diagnosis is often challenging due to difficultly obtaining diagnostic respiratory specimens, which may contain low concentrations of Mycobacterium tuberculosis (Mtb) bacilli. However, we have reported that an immuno-affinity liquid chromatography-tandem mass spectrometry TB assay (ILM-TB) that detects a peptide derived from Mtb 10-kDa culture filtrate protein (CFP10pep) can diagnose TB regardless of patient age or infection site when analyzing trypsin-digested blood samples.
Methods Discovery and validation cohorts were respectively generated from children who consecutively presented at two hospitals in South Africa (SA) from April 2012 to August 2017 (157 children <13 years-of-age) or at two communities in the Dominican Republic (DR) from July 2019 to May 2023 (101 children <17 years-of-age). All children were evaluated for TB at enrollment and 6-months post-enrollment, and assigned confirmed, unconfirmed, or unlikely TB diagnoses based on the 2015 NIH criteria for pediatric TB. Serum samples were collected at and two and six months after SA/DR enrollment, and at two weeks DR post-enrollment (270 SA and 304 DR samples) to evaluate ILM-TB assay performance.
Findings SA and DR serum ILM-TB results had comparable sensitivity (82·9% and 84·4%) to respiratory culture and Xpert for confirmed TB, and robust sensitivity (80·5% and 76·5%) for unconfirmed TB, with differential specificity for unlikely TB cases with and without TB consistent symptoms (78·4–98·1%). CFP10pep levels decreased by six months post-treatment initiation only in children with positive treatment responses.
Interpretation Serum CFP10pep detection can effectively diagnose pediatric TB, including unconfirmed and extrapulmonary TB cases missed by sputum-based methods, while decreases after treatment anti-TB treatment initiation can monitoring effective treatment responses.
2025-10-01 | PXD053274 | panorama
Project description:The diagnosis of pediatric tuberculosis (TB) poses a challenge for clinical teams worldwide. TB-mediated changes in the expression of host genes in the peripheral blood can serve as diagnostic biomarkers and can provide better insights into the host immune mechanisms of childhood TB. Peripheral blood mononuclear cells (PBMCs) from children (n=102) with microbiologically confirmed TB disease, ΤΒ infection (ΤΒΙ), pneumonia, and healthy controls (HC) were stimulated with either the Purified Protein Derivative (PPD) or the Early Secretory Antigen 6kDa-Culture Filtrate Protein 10 (ESAT6-CFP10) complex of Mycobacterium tuberculosis (Mtb). RNA was extracted and quantified using gene expression microarrays. Differential expression analysis was performed comparing microbiologically confirmed TB to the other diagnostic groups for the stimulated and unstimulated samples. Using variable selection, we identified sparse diagnostic gene signatures; one gene (PID1) was able to distinguish TB from pneumonia after ESAT6-CFP10 stimulation with an AUC of 100% in the test set, while a combination of two genes (STAT1 and IFI44) achieved an AUC of 91.7% (CI95% 75.0%-100%) in the test set after PPD stimulation. The number of significantly differentially expressed (SDE) genes was higher when contrasting TB to pneumonia or HC in stimulated samples, compared to unstimulated ones, leading to a larger pool of candidate diagnostic biomarkers. Our approach provides enlightened aspects of peripheral TB-specific responses and can form the basis for a point of care test meeting the World Health Organization (WHO) Target Product Profile (TPP) for pediatric TB.
2024-10-16 | GSE249575 | GEO
Project description:Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that represents a zoonotic threat to humans. Research has shown that the peripheral blood (PB) transcriptome is perturbed during bTB disease but the genomic architecture underpinning this transcriptional response remains poorly understood. Here, we analyse PB transcriptomics data from 63 control and 60 confirmed M. bovis infected animals and detect 2,592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis¬-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during M. bovis infection. Integrating our cis-eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 132 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.
2024-02-26 | GSE255724 | GEO
Project description:Tuberculosis (TB) is a serious infectious disease, but current methods of detection require improvement in sensitivity, efficiency or specificity. We conducted a microarray experiment, comparing the gene expression profiles in peripheral blood mononuclear cells among individuals with active TB, latent infection, and healthy conditions in a Taiwanese population. These differentially expressed genes may be potential biomarkers that can differentiate between active TB and latent infection.
2014-10-21 | GSE62525 | GEO
Project description:Background: Atopic dermatitis (AD) predominantly affects young children, but our understanding of AD pathogenesis is based on skin and blood samples from longstanding adult AD. Genomic biopsy profiling from early pediatric AD showed significant Th2 and Th17/Th22-skewing, without the characteristic adult Th1 up-regulation. Since obtaining pediatric biopsies is difficult, blood gene expression profiling may provide a surrogate for the pediatric skin signature. Objective: To define the blood profile and associated biomarkers of early moderate-to-severe pediatric AD. Methods: We compared microarrays and RT-PCR of blood cells from 28 AD children (<5yrs and within 6 months of disease onset) to healthy control blood cells. Differentially expressed genes/DEGs in blood (fold change/FCH>1.2 and false discovery rate/FDR<0.05) were then compared with skin DEGs. Results: Eosinophil and Th2 markers (IL5RA, IL1RL1/ST2, HRH4, CCR3, SIGLEC8, PRSS33, CLC from gene arrays; IL13/IL4/CCL22 from RT-PCR) were upregulated in early pediatric AD blood, while IFNG/Th1 was decreased. Th1 markers were negatively correlated with clinical severity (EASI, pruritus, transepidermal water loss/TEWL), whereas Th2/Th17-induced IL19 was positively correlated with SCORAD. While a few RT-PCR-defined immune markers (IL13/CCL22) were increased in blood, as previously also reported for skin, there was minimal overlap based on gene array DEGs. Conclusion: The whole blood signature of early moderate-to-severe pediatric AD blood cells show predominantly a Th2/eosinophil profile, but markers largely differ from the skin profile. Given their complementarity, pooling of biomarkers from blood and skin may improve profiling and predictions, providing insight regarding disease course allergic comorbidity development, and response to systemic medications.
2018-12-06 | GSE116486 | GEO
Project description:Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle
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