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

Shajo Kunnath-Velayudhan, Amy L. Davidow, Hui Yun Wang, Douglas M. Molina, Vu T. Huynh, Hugh Salamon, Richard Pine, Gerd Michel, Mark D. Perkins, Liang Xiaowu, Philip L. Felgner, Joanne L. Flynn, Antonino Catanzaro, Maria L. Gennaro

Research output: Contribution to journalArticle

46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)697-705
Number of pages9
JournalJournal of Infectious Diseases
Volume206
Issue number5
DOIs
StatePublished - Sep 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Proteome-scale antibody responses and outcome of mycobacterium tuberculosis infection in nonhuman primates and in tuberculosis patients'. Together they form a unique fingerprint.

  • Cite this

    Kunnath-Velayudhan, S., Davidow, A. L., Wang, H. Y., Molina, D. M., Huynh, V. T., Salamon, H., Pine, R., Michel, G., Perkins, M. D., Xiaowu, L., Felgner, P. L., Flynn, J. L., Catanzaro, A., & Gennaro, M. L. (2012). Proteome-scale antibody responses and outcome of mycobacterium tuberculosis infection in nonhuman primates and in tuberculosis patients. Journal of Infectious Diseases, 206(5), 697-705. https://doi.org/10.1093/infdis/jis421