Jun 27, 2012

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

The Journal of Infectious Diseases
Shajo Kunnath-VelayudhanMaria L Gennaro

Abstract

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. 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. 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. Integration of macaque and human data reveals dynamic properties of antibody responses in relation to o...Continue Reading

Mentioned in this Paper

Nonhuman primate
Tuberculosis
Latent Infection
Phosphoglycerate Dehydrogenase Activity
Antibody Formation
Proteomics
Proteome
Sputum
PHGDH wt Allele
Mycobacterium tuberculosis H37Rv

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