Dataset Information

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

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Publications

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

Kwan Philip Kam Weng PKW Periaswamy Balamurugan B De Sessions Paola Florez PF Lin Wenwei W Molton James S JS Naftalin Claire M CM Naim Ahmad Nazri Mohamed ANM Hibberd Martin L ML Paton Nicholas I NI

BMC infectious diseases 20200609 1

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 32517725

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Project description:BackgroundComorbidities such as undernutrition and parasitic infections are widespread in India and other tuberculosis (TB)-endemic countries. This study examines how these conditions as well as food supplementation and parasite treatment might alter immune responses to Mycobacterium tuberculosis (Mtb) infection and risk of progression to TB disease.MethodsThis is a 5-year prospective clinical trial at Jawaharlal Institute of Post Graduate Medical Education and Research in Puducherry, Tamil Nadu, India. We aim to enroll 760 household contacts (HHC) of adults with active TB in order to identify 120 who are followed prospectively for 2 years: Thirty QuantiFERON-TB Gold Plus (QFT-Plus) positive HHCs ≥ 18 years of age in four proposed groups: (1) undernourished (body mass index [BMI] < 18.5 kg/m2); (2) participants with a BMI ≥ 18.5 kg/m2 who have a parasitic infection (3) undernourished participants with a parasitic infection and (4) controls-participants with BMI ≥ 18.5 kg/m2 and without parasitic infection. We assess immune response at baseline and after food supplementation (for participants with BMI < 18.5 kg/m2) and parasite treatment (for participants with parasites). Detailed nutritional assessments, anthropometry, and parasite testing through polymerase chain reaction (PCR) and microscopy are performed. In addition, at serial time points, these samples will be further analyzed using flow cytometry and whole blood transcriptomics to elucidate the immune mechanisms involved in disease progression.ConclusionsThis study will help determine whether undernutrition and parasite infection are associated with gene signatures that predict risk of TB and whether providing nutritional supplementation and/or treating parasitic infections improves immune response towards this infection. This study transcends individual level care and presents the opportunity to benefit the population at large by analyzing factors that affect disease progression potentially reducing the overall burden of people who progress to TB disease. Trial registration ClinicalTrials.gov; NCT03598842; Registered on July 26, 2018; https://clinicaltrials.gov/ct2/show/NCT03598842.

Dataset Information

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

Background

Methods

Conclusions

Publications

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

Similar Datasets

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