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. 2016 Sep;73(3):219-30.
doi: 10.1016/j.jinf.2016.04.036. Epub 2016 Jun 14.

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

Dolapo O Awoniyi  1 , Andrea Teuchert  1 , Jayne S Sutherland  2 , Harriet Mayanja-Kizza  3 , Rawleigh Howe  4 , Adane Mihret  4 , Andre G Loxton  1 , Jacob Sheehama  5 , Desta Kassa  6 , Amelia C Crampin  7 , Hazel M Dockrell  8 , Martin Kidd  9 , Ida Rosenkrands  10 , Annemieke Geluk  11 , Tom H M Ottenhoff  11 , P L A M Corstjens  12 , Novel N Chegou  1 , Gerhard Walzl  13 ; AE-TBC Consortium
Collaborators, Affiliations
Free article

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

Dolapo O Awoniyi et al. J Infect. 2016 Sep.
Free article

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.

Keywords: Antigen; Biosignature; Host markers.

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