Dynamic antibody responses to the Mycobacterium tuberculosis proteome.

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.

authors

Kunnath-Velayudhan S,Salamon H,Wang HY,Davidow AL,Molina DM,Huynh VT,Cirillo DM,Michel G,Talbot EA,Perkins MD,Felgner PL,Liang X,Gennaro ML

doi

10.1073/pnas.1009080107

subject

Has Abstract

pub_date

2010-08-17 00:00:00

pages

14703-8

issue

33

eissn

0027-8424

issn

1091-6490

pii

1009080107

journal_volume

107

pub_type

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