دورية أكاديمية
أعرض في EDS

A blood RNA transcript signature for TB exposure in household contacts.

التفاصيل البيبلوغرافية
العنوان: A blood RNA transcript signature for TB exposure in household contacts.
المؤلفون: Kwan PKW; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore., Periaswamy B; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore., De Sessions PF; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore., Lin W; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore., Molton JS; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore., Naftalin CM; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore., Naim ANM; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore., Hibberd ML; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.; London School of Hygiene & Tropical Medicine, London, UK.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Paton NI; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore. nick_paton@nuhs.edu.sg.; London School of Hygiene & Tropical Medicine, London, UK. nick_paton@nuhs.edu.sg.
المصدر: BMC infectious diseases [BMC Infect Dis] 2020 Jun 09; Vol. 20 (1), pp. 403. Date of Electronic Publication: 2020 Jun 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 100968551 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2334 (Electronic) Linking ISSN: 14712334 NLM ISO Abbreviation: BMC Infect Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2001-
مواضيع طبية MeSH: Latent Tuberculosis/*diagnosis , RNA/*blood, Adult ; Aged ; Basic-Leucine Zipper Transcription Factors/genetics ; Case-Control Studies ; Contact Tracing ; Female ; Humans ; Interferon Type I/metabolism ; Latent Tuberculosis/microbiology ; Latent Tuberculosis/transmission ; Male ; Middle Aged ; Neutrophils/immunology ; Neutrophils/metabolism ; Protein Interaction Maps/genetics ; RNA/chemistry ; RNA/metabolism ; Scavenger Receptors, Class F/genetics ; Tumor Suppressor Proteins/genetics ; Young Adult
مستخلص: Background: Current tools for diagnosing latent TB infection (LTBI) detect immunological memory of past exposure but are unable to determine whether exposure is recent. We sought to identify a whole-blood transcriptome signature of recent TB exposure.
Methods: We studied household contacts of TB patients; healthy volunteers without recent history of TB exposure; and patients with active TB. We performed whole-blood RNA sequencing (in all), an interferon gamma release assay (IGRA; in contacts and healthy controls) and PET/MRI lung scans (in contacts only). We evaluated differentially-expressed genes in household contacts (log2 fold change ≥1 versus healthy controls; false-discovery rate < 0.05); compared these to differentially-expressed genes seen in the active TB group; and assessed the association of a composite gene expression score to independent exposure/treatment/immunological variables.
Results: There were 186 differentially-expressed genes in household contacts (n = 26, age 22-66, 46% male) compared with healthy controls (n = 5, age 29-38, 100% male). Of these genes, 141 (76%) were also differentially expressed in active TB (n = 14, age 27-69, 71% male). The exposure signature included genes from inflammatory response, type I interferon signalling and neutrophil-mediated immunity pathways; and genes such as BATF2 and SCARF1 known to be associated with incipient TB. The composite gene-expression score was higher in IGRA-positive contacts (P = 0.04) but not related to time from exposure, isoniazid prophylaxis, or abnormalities on PET/MRI (all P > 0.19).
Conclusions: Transcriptomics can detect TB exposure and, with further development, may be an approach of value for epidemiological research and targeting public health interventions.
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معلومات مُعتمدة: NMRC/TCR/011-NUHS/2014 National Medical Research Council; NMRC/CSA/0050/2013 National Medical Research Council; NMRC/CG/013/2013 National Medical Research Council
فهرسة مساهمة: Keywords: Biomarkers; TB exposure; TB infection; RNA sequencing; Tuberculosis; gene expression; Whole blood
المشرفين على المادة: 0 (Basic-Leucine Zipper Transcription Factors)
0 (Batf2 protein, human)
0 (Interferon Type I)
0 (SCARF1 protein, human)
0 (Scavenger Receptors, Class F)
0 (Tumor Suppressor Proteins)
63231-63-0 (RNA)
تواريخ الأحداث: Date Created: 20200611 Date Completed: 20200713 Latest Revision: 20210225
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC7282166
DOI: 10.1186/s12879-020-05116-1
PMID: 32517725
قاعدة البيانات: MEDLINE
الوصف
تدمد:1471-2334
DOI:10.1186/s12879-020-05116-1