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.
journal_name
Proc Natl Acad Sci U S Aauthors
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 MLdoi
10.1073/pnas.1009080107subject
Has Abstractpub_date
2010-08-17 00:00:00pages
14703-8issue
33eissn
0027-8424issn
1091-6490pii
1009080107journal_volume
107pub_type
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