Dynamic antibody responses to the Mycobacterium tuberculosis proteome

Shajo Kunnath-Velayudhan, Hugh Salamon, Hui Yun Wang, Amy L. Davidow, Douglas M. Molina, Vu T. Huynh, Daniela M. Cirillo, Gerd Michel, Elizabeth A. Talbot, Mark D. Perkins, Philip L. Felgner, Xiaowu Liang, Maria L. Gennaro

Research output: Contribution to journalArticle

Abstract

Considerable effort has been directed toward controlling tuberculosis, which kills almost two million people yearly. High on the research agenda is the discovery of biomarkers of active tuberculosis (TB) for diagnosis and for monitoring treatment outcome. Rational biomarker discovery requires understanding host-pathogen interactions leading to biomarker expression. Here we report a systems immunology approach integrating clinical data and bacterial metabolic and regulatory information with high-throughput detection in human serum of antibodies to the entire Mycobacterium tuberculosis proteome. Sera from worldwide TB suspects recognized approximately 10% of the bacterial proteome. This result defines the M. tuberculosis immunoproteome, which is rich in membrane-associated and extracellular proteins. Additional analyses revealed that during active tuberculosis (i) antibody responses focused on an approximately 0.5% of the proteome enriched for extracellular proteins, (ii) relative target preference varied among patients, and (iii) responses correlated with bacillary burden. These results indicate that the B cell response tracks the evolution of infection and the pathogen burden and replicative state and suggest functions associated with B cell-rich foci seen in tuberculous lung granulomas. Our integrated proteome-scale approach is applicable to other chronic infections characterized by diverse antibody target recognition.

Original languageEnglish
Pages (from-to)14703-14708
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number33
DOIs
Publication statusPublished - Aug 17 2010

Keywords

  • Biomarkers
  • Granuloma
  • Humoral immunity
  • Protein microarray

ASJC Scopus subject areas

  • General

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    Kunnath-Velayudhan, S., Salamon, H., Wang, H. Y., Davidow, A. L., Molina, D. M., Huynh, V. T., Cirillo, D. M., Michel, G., Talbot, E. A., Perkins, M. D., Felgner, P. L., Liang, X., & Gennaro, M. L. (2010). Dynamic antibody responses to the Mycobacterium tuberculosis proteome. Proceedings of the National Academy of Sciences of the United States of America, 107(33), 14703-14708. https://doi.org/10.1073/pnas.1009080107