In vitro profiling of mycobacterium tuberculosis region of difference 1 antigen induced cytokine and chemokines production among patients with active pulmonary tuberculosis and latent tuberculosis
Introduction: Tuberculosis (TB) is one of the leading causes of death worldwide and human immunodeficiency virus (HIV) co-infection poses a great challenge in its control. Furthermore, diagnosis ofTB in HIV co-infected subjects is not easy. Early diagnosis of TB is important in the control ofTB both for treatment of patients and curbing transmission to others in the community. In countries like Kenya where the prevalence of HIV is higher than 5% in the general population. there is need to identify a biomarker that can be used to accurately diagnose Mycobacteria tuberculosis infection. A diagnostic technique that can differentiate between active TB and latent IB infection (L TBI) would also be a major breakthrough. Objective: The aim of this study was to identify specific M tuberculosis CFP-I0 and ESAT-6 induced cytokine(s) and chemokine(s) that are consistently present amongst patients with latent and active tuberculosis regardless of their immune status and that can discriminate L TBI from active TB disease. Design: This was a cross-sectional study. Methodology: A total of 82 subjects were recruited into the study of which 62(75.6%) were pulmonary TB patients, 13 (15.86%) were household contacts (HHC) and 7(8.54%) were controls from another ongoing study. Luminex multiplex cytokine assay was performed to determine the levels of 17 cytokines/chemokines in QFT supernatants. The quantity of cytokine produced following stimulation with ESAT-6 and CFP-IO (antigen-dependent cytokine and chemokine) was determined by subtracting the concentration of cytokine in the nil tube from the antigen tube. Results: Interleukin 2, IFNy and ILIra were produced in significantly high amounts in ESAT 6 and CFP 10 stimulated whole blood from Mtuberculosis infected compared to controls who were quantiFERONﾮ TB Gold negative and HIV negative. Interleukin 17 was consistently produced in significantly lower amount in those participants with active TB regardless of the HIV status compared to controls. Interleukin lu, IL2, MIPIa and TNFa were produce in significantly higher amounts in ESA T 6 and CFP 1o stimulated whole blood from participants with latent TB infection (L TBI) compared to active TB. Conclusion: Interferon gamma, IL2, ILlra and ILl7 can be useful biomarkers of TB. However, IFNy, IL2 and ILlra cannot be relied on in the diagnosis of TBamong HIV patients especially those who are severely immunosuppressed. Interleukin 2, MIPla, and ILIa have poor sensitivity in discriminating active TB and LTBI and therefore they cannot be used individually. Further studies are needed to explore the potential IL2, ILlra, ILI7, ILIa, MIPI~, MIPI~ and TNFa individually and in combination in diagnosis of M tuberculosis infection and in discriminating L TBI and active TB.