Dolapo O Awoniyi1, Andrea Teuchert1, Jayne S Sutherland2, Harriet Mayanja-Kizza3, Rawleigh Howe4, Adane Mihret4, Andre G Loxton1, Jacob Sheehama5, Desta Kassa6, Amelia C Crampin7, Hazel M Dockrell8, Martin Kidd9, Ida Rosenkrands10, Annemieke Geluk11, Tom H M Ottenhoff11, P L A M Corstjens12, Novel N Chegou1, Gerhard Walzl13. 1. Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, Cape Town, South Africa. 2. Medical Research Council Unit, Fajara, Gambia. 3. Department of Medicine, Makerere University, Kampala, Uganda. 4. Armauer Hansen Research Institute, Addis Ababa, Ethiopia. 5. University of Namibia, Faculty of Health Sciences, School of Medicine, Namibia. 6. Ethiopian Health and Nutrition Research Institute, Addis Ababa, Ethiopia. 7. Karonga Prevention Study, Chilumba, Malawi; London School of Hygiene and Tropical Medicine, London, UK. 8. London School of Hygiene and Tropical Medicine, London, UK. 9. Centre for Statistical Analysis, Stellenbosch University, South Africa. 10. Statens Serum Institut, Copenhagen, Denmark. 11. Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands. 12. Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands. 13. Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, Cape Town, South Africa. Electronic address: gwalzl@sun.ac.za.
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.
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.
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