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Title: A blood RNA transcript signature for TB exposure in household contacts
Authors: Kwan, P.K.W. 
Periaswamy, B. 
De Sessions, P.F.
Lin, W. 
Molton, J.S. 
Naftalin, C.M.
Naim, A.N.M.
Hibberd, Martin L. 
Paton, N.I. 
Keywords: Biomarkers
TB exposure
TB infection
RNA sequencing
gene expression
Whole blood
Issue Date: 2020
Publisher: BioMed Central Ltd
Citation: Kwan, P.K.W., Periaswamy, B., De Sessions, P.F., Lin, W., Molton, J.S., Naftalin, C.M., Naim, A.N.M., Hibberd, Martin L., Paton, N.I. (2020). A blood RNA transcript signature for TB exposure in household contacts. BMC Infectious Diseases 20 (1) : 403. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: 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. � 2020 The Author(s).
Source Title: BMC Infectious Diseases
ISSN: 14712334
DOI: 10.1186/s12879-020-05116-1
Rights: Attribution 4.0 International
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