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

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 h 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.

More information

Type
Journal Article
Author
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 M
Corstjens P L A M
Chegou NN
Walzl G
Year of Publication
2016
Journal
The Journal of infection
Volume
73
Issue
3
Number of Pages
219-30
Language
eng
ISSN Number
1532-2742
DOI
10.1016/j.jinf.2016.04.036
Alternate Journal
J. Infect.
Publication Language
eng