Kwan, Philip Kam Weng; Periaswamy, Balamurugan; De Sessions, Paola Florez; Lin, Wenwei; Molton, James S; Naftalin, Claire M; Naim, Ahmad Nazri Mohamed; Hibberd, Martin L; Paton, Nicholas I; (2020) A blood RNA transcript signature for TB exposure in household contacts. BMC INFECTIOUS DISEASES, 20 (1). 403-. ISSN 1471-2334 DOI: https://doi.org/10.1186/s12879-020-05116-1
Permanent Identifier
Use this Digital Object Identifier when citing or linking to this resource.
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.
Item Type | Article |
---|---|
Faculty and Department | Faculty of Infectious and Tropical Diseases > Department of Infection Biology |
Research Centre | TB Centre |
PubMed ID | 32517725 |
Elements ID | 148295 |
Download
Filename: A blood RNA transcript signature for TB exposure in household contacts.pdf
Licence: Creative Commons: Attribution 3.0
Download