In:
BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1471-2334
DOI:
10.1186/s12879-020-05116-1
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2020
ZDB Id:
2041550-3
