Dataset Information

Proteome-scale antibody responses and outcome of Mycobacterium tuberculosis infection in nonhuman primates and in tuberculosis patients.

ABSTRACT:

Background

Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies.

Methods

Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression.

Results

Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome.

Conclusions

Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.

SUBMITTER: Kunnath-Velayudhan S

PROVIDER: S-EPMC3491745 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Publications

Proteome-scale antibody responses and outcome of Mycobacterium tuberculosis infection in nonhuman primates and in tuberculosis patients.

Kunnath-Velayudhan Shajo S Davidow Amy L AL Wang Hui-Yun HY Molina Douglas M DM Huynh Vu T VT Salamon Hugh H Pine Richard R Michel Gerd G Perkins Mark D MD Xiaowu Liang L Felgner Philip L PL Flynn JoAnne L JL Catanzaro Antonino A Gennaro Maria L ML

The Journal of infectious diseases 20120625 5

<h4>Background</h4>Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies.<h4>Methods</h4>Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescenc ...[more]

PMID: 22732925

Similar Datasets

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.

Dataset Information

Proteome-scale antibody responses and outcome of Mycobacterium tuberculosis infection in nonhuman primates and in tuberculosis patients.

Background

Methods

Results

Conclusions

Publications

Proteome-scale antibody responses and outcome of Mycobacterium tuberculosis infection in nonhuman primates and in tuberculosis patients.

Similar Datasets

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