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

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?ResultsThere 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.

SUBMITTER: Kwan PKW 

PROVIDER: S-EPMC7282166 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature