Identification of Host Proteins Predictive of Early Stage Mycobacterium tuberculosis Infection

Abstract The objective of this study was to identify blood-based protein biomarkers of early stage Mycobacterium tuberculosis ( Mtb ) infection. We utilized plasma and serum specimens from TB patients and their contacts (age ≥ 12) enrolled in a household contact study in Uganda. In the discovery phase cross-sectional samples from 104 HIV-uninfected persons classified as either active TB, latent Mtb infection (LTBI), tuberculinskin test (TST) converters, or persistent TST-negative were analyzed. Two hundred eighty-nine statistically significant ( false discovery ratecorrected p Mtb infection. One hundred and fifty-nine proteins were selected for a targeted mass spectrometryassay. A set of longitudinal samples from 52 TST-negative subjects who converted to TST-positive or remained TST-negative were analyzed, and multivariate logistic regression was used to identify unique protein panels able to predict TST conversion with cross-validated AUC > 0.85. Panel performance was confirmed with an independent validation set of longitudinal samples from 16 subjects. These candidate protein biomarkers may allow for the identification of recently Mtb infected individuals at highest risk for developing active TB and most likely to benefit from preventive therapy.