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Genome-wide analysis of blood gene expression profile at diagnosis and post treatment in latent TB and active TB subjects

ABSTRACT: Changes in the blood transcriptome upon treatment were studied in a cohort of 42 latent tuberculosis (TB) subjects and 8 active TB subiects. Samples were collected at diagnosis (prior the start of treatment) and post treatment and gene expression studied with Illumina microarrays. We hypothesize that individuals with latent TB at risk of developing active disease are immunologically closer to those with active TB and will thus display a blood transcriptomic signature similar to active TB subjects upon treatment. This signature should significantly differ from the one mounted by latent TB individuals at low risk of progression. Thus, monitoring blood transcriptomic changes following anti-TB therapy might inform on which latent TB subjects should be prioritized for receiving therapeutic intervention in order to prevent further transmission.

ORGANISM(S): Homo sapiens

PROVIDER: GSE152532 | GEO | 2021/12/08

REPOSITORIES: GEO

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Project description:Human infection with Mycobacterium tuberculosis results in a continuum of ill-defined, clinical manifestations with stable latent M. tuberculosis infection (LTBI) and severe active disease at the ends. Identifying different states of infection is of importance to tuberculosis (TB) control since risk of developing active disease varies among different asymptomatic states while infectiousness varies among patients with different bacterial burden. We investigated changes in proteome-scale antibody responses during disease progression in a non-human primate model of tuberculosis. We probed M. tuberculosis proteome microarrays with serial sera collected from three infection-outcome groups (active, reactivation, and latent). We found that each infection outcome is associated with characteristic changes in the antibody levels and number of antigenic targets, which suggested an association between antibody responses and bacillary burden. Additional proteome-scale serological profiling of > 400 human TB suspects established that antibody responses are positively associated with bacterial load. Thus tuberculosis-specific antibody levels and number of antigenic targets increases with disease progression. Serum samples collected from adult patients with suspected tuberculosis during a multi-site study was used to probe whole proteome microarrays. Subject recruitment was conducted under uniform protocols approved by the institutional ethics committee at each site. Final diagnosis of active TB was based on positive M. tuberculosis culture results. The active TB patients were further subdivided into smear-positive and negative disease based on results of Ziehl-Neelsen staining of sputum smears for acid fast bacilli. Active TB was excluded as a diagnosis (Non-TB Disease [NTBD] patients) based on having negative M. tuberculosis culture and smear results and on having an alternate diagnosis. All subjects were presumably negative for HIV infection given the very low incidence of HIV infection in the study sites. Sera from 169 TB and 242 NTBD patients were selected for microarray probing. The control sera (n = 14) which was used to generate negative control distribution for each protein were negative to latent M. tuberculosis infection, as indicated by negative results to tuberculin skin test.

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Genome-wide analysis of blood gene expression profile at diagnosis and post treatment in latent TB and active TB subjects

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