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Evaluation of cytokine responses against novel Mtb antigens as diagnostic markers for TB disease.

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Awoniyi DO, Teuchert A, Sutherland JS, Mayanja-Kizza H, Howe R, Mihret A, Loxton AG, Sheehama J, Kassa D, Crampin AC, Dockrell HM, Kidd M, Rosenkrands I, Geluk A, Ottenhoff TH, Corstjens PL, Chegou NN, Walzl G, ,


Awoniyi DO, Teuchert A, Sutherland JS, Mayanja-Kizza H, Howe R, Mihret A, Loxton AG, Sheehama J, Kassa D, Crampin AC, Dockrell HM, Kidd M, Rosenkrands I, Geluk A, Ottenhoff TH, Corstjens PL, Chegou NN, Walzl G, , (click to view)

Awoniyi DO, Teuchert A, Sutherland JS, Mayanja-Kizza H, Howe R, Mihret A, Loxton AG, Sheehama J, Kassa D, Crampin AC, Dockrell HM, Kidd M, Rosenkrands I, Geluk A, Ottenhoff TH, Corstjens PL, Chegou NN, Walzl G, ,

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The Journal of infection 2016 6 13() pii 10.1016/j.jinf.2016.04.036

Abstract
OBJECTIVE
We investigated the accuracy of host markers detected in Mtb antigen-stimulated whole blood culture supernatant in the diagnosis of TB.

METHODS
Prospectively, blood from 322 individuals with presumed TB disease from six African sites was stimulated with four different Mtb antigens (Rv0081, Rv1284, ESAT-6/CFP-10, and Rv2034) in a 24 hour whole blood stimulation assay (WBA). The concentrations of 42 host markers in the supernatants were measured using the Luminex multiplex platform. Diagnostic biosignatures were investigated through the use of multivariate analysis techniques.

RESULTS
17% of the participants were HIV infected, 106 had active TB disease and in 216 TB was excluded. Unstimulated concentrations of CRP, SAA, ferritin and IP-10 had better discriminating ability than markers from stimulated samples. Accuracy of marker combinations by general discriminant analysis (GDA) identified a six analyte model with 77% accuracy for TB cases and 84% for non TB cases, with a better performance in HIV uninfected patients.

CONCLUSIONS
A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance.

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