Research Project
6986656
DESCRIPTION (provided by applicant): A large body of evidence supports the idea that expression of host adaptive immunity may cause Mycobacterium tuberculosis to enter a dormant state that establishes latent infection. Subsequent impairment of the immune response can allow tubercle bacilli to resume multiplication and cause reactivation disease. We have observed that in humans the antibody profile associated with active disease differs from that associated with latent infection. We have also found that in mice expression of host immunity is accompanied by an apparent change in growth rate and by changes in transcription of bacterial genes encoding immunodominant antigens. Together, these data lead to the hypothesis that antibody profiles vary during human infection, presumably in relation to changes of bacterial antigen composition occurring in response to host immune status. If this hypothesis is correct, changes in antibody profiles can be an indirect marker of bacterial antigen change and infection outcome. An initial test of the hypothesis will be conducted in an area of Cape Town, South Africa characterized by high tuberculosis prevalence and relatively low HIV prevalence. Sera have already been obtained from persons in four diagnostic groups: active tuberculosis, latent M. tuberculosis infection with and without chest X-ray abnormalities, and uninfected controls. Two aims are proposed. First, established, high-throughput methods will be used to generate a >200-protein microarray chip of M. tuberculosis suited for serological screens. Second, antibody profiles most characteristic of tuberculosis state will be identified by screening the protein microarray with sera from the four, above-defined diagnostic groups. Those antibody profiles will be correlated with outcome of M. tuberculosis infection in future, longitudinal studies in the same study area. The proposed work will lead to identifying serological markers of progression to active tuberculosis that are detectable before clinical or bacteriological markers of active disease.
