Proteome-scale antibody responses and outcome of Mycobacterium tuberculosis infection in nonhuman primates and in tuberculosis patients.
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.
Public Health Research Institute, New Jersey Medical School, 225 Warren St, Newark, New Jersey 07103, USA.
Shajo
S
Kunnath-Velayudhan
Amy L
AL
Davidow
Hui-Yun
HY
Wang
Douglas M
DM
Molina
Vu T
VT
Huynh
Hugh
H
Salamon
Richard
R
Pine
Gerd
G
Michel
Mark D
MD
Perkins
Liang
L
Xiaowu
Philip L
PL
Felgner
JoAnne L
JL
Flynn
Antonino
A
Catanzaro
Maria L
ML
Gennaro
D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D006801:Humans; D008252:Macaca fascicularis; D008875:Middle Aged; D008992:Monkey Diseases / Q000276:immunology* / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D040081:Protein Array Analysis; D020543:Proteome / Q000276:immunology*; D040901:Proteomics / Q000379:methods; D012044:Regression Analysis; D012189:Retrospective Studies; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology*
D000907:Antibodies, Bacterial; D015415:Biomarkers; D020543:Proteome