Tuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interferon gamma (IFN-γ), Interferon gamma-induced protein 10 (IP-10), Interleukin-2 receptor (IL-2R), C-X-C Motif Chemokine Ligand 9 (CXCL-9), Interleukin 10 (IL-10), Interleukin 4 (IL-4), and Tumor Necrosis Factor alpha (TNF-α)) in response to tuberculosis antigen was analyzed using real-time polymerase reaction. The sensitivity and specificity of relative quantification (2^-ΔΔCt) of mRNA expression were analyzed by constructing receiver operating characteristic curves and measuring the area under the curve (AUC) values. Combinations of cytokines were analyzed using the R statistical software package. IFN-γ, IP-10, IL2R, and CXCL-9 showed high expression in latent and active tuberculosis patients (p = 0.001), with a decrease in IL10 expression, and no statistical difference in IL-4 levels among all the groups (p = 0.999). IL-10 differentiated pulmonary tuberculosis patients from latent cases with an AUC of 0.731. IL10 combined with CXCL-9 distinguished pulmonary tuberculosis patients from extrapulmonary cases with a sensitivity, specificity, and accuracy of 85.7%, 73.9%, and 81.0%, respectively. IL-10 together with IP-10 and IL-4 differentiated pulmonary tuberculosis from latent cases with a sensitivity and specificity of 77.1% and 88.1%, respectively. Decision tree analysis demonstrated that IFN-γ IL-2R, and IL-4 can diagnose tuberculosis infection with a sensitivity, specificity, and accuracy of 89.7%, 96.1%, and 92.7%, respectively. A combination of gene expression of cytokines and chemokines might serve as an effective marker to differentiate tuberculosis infection state(s).
|Publication status||Published - 2020 Sept|
Bibliographical noteFunding Information:
Funding: This study is part of the research funded by the National Research Foundation, Joint research program, Republic of Korea (Grant Number = NFR-2017K2A9A1A01092944).
This study is part of the research funded by the National Research Foundation, Joint research program, Republic of Korea (Grant Number = NFR-2017K2A9A1A01092944). We are grateful to Taye Balcha (Armaure Hansen Research Institute) for his genuine support and for creating the platform for collaboration. We also acknowledge individuals and professionals who assisted in sample collection and transportation: Tigist Damitew and Tirsit Ayalew (Zewuditu Memorial Hospital); Abebayew Minalu and Nesira Kedir (Tekilehaymahot Health Station); Fantanesh Melese, Yayehyirad Tassachew, Emawayish Andargie, Henok Andualem, Dawit Beyene, Dawit Tayachew, and Daniel Demissu (Armaure Hansen Research Institute); Ahmed Musa (Girar Health Station); Kelemua Zewude and Tesfu Melaku (St. Paul?s Hospital Millennium Medical College, Department of Pathology).
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
All Science Journal Classification (ASJC) codes
- Clinical Biochemistry