Profiling proteome-scale antibody responses to M. tuberculosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Shajo Kunnath-Velayudhan
PROVIDER: E-GEOD-31368 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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]
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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.
2012-07-05 | E-GEOD-30722 | biostudies-arrayexpress
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. To investigate antibody responses during the course of infection, we probed M. tuberculosis proteome microarrays with serial sera collected from experimentally infected cynomolgus macaques. Based on infection outcome, the macaques were grouped into three classes; A) active disease (n = 4), B) latent infection (n=5) and C) reactivation disease (n = 5). Note that the macaques in the reactivation class developed signs of disease spontaneously without any experimental intervention. For each animal, we tested one pre-infection time point and approximately ten post-infection time points at one-month intervals.
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